The c.5563delAinsGGATCC variant, located in coding exon 22 of the BRCA1 gene, results from the deletion of one nucleotide and insertion of 6 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.I1855Gfs*69). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of BRCA1, is not expected to trigger nonsense-mediated mRNA decay, and results in the elongation of the protein by 58 amino acids. The exact functional impact of these inserted amino acids is unknown at this time. One functional study found that this alteration impaired BRCA1 transcriptional activation activity (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5563delinsGGATCC (p.Ile1855fs)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(2)
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Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Conflicting classifications of pathogenicity
Likely pathogenic(1); Uncertain significance(1)
Likely pathogenic(1); Uncertain significance(1)
2
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5563delinsGGATCC (p.Ile1855fs)
Variation ID: 825830 Accession: VCV000825830.10
- Type and length
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Indel, 6 bp
- Location
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Cytogenetic: 17q21.31 17: 43045707 (GRCh38) [ NCBI UCSC ] 17: 41197724 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Mar 16, 2020 May 1, 2024 Jan 30, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5563delinsGGATCC MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ile1855fs frameshift NM_001407571.1:c.5350delAinsGGATCC NP_001394500.1:p.Ile1784Glyfs frameshift NM_001407581.1:c.5629delAinsGGATCC NP_001394510.1:p.Ile1877Glyfs frameshift NM_001407582.1:c.5629delAinsGGATCC NP_001394511.1:p.Ile1877Glyfs frameshift NM_001407583.1:c.5626delAinsGGATCC NP_001394512.1:p.Ile1876Glyfs frameshift NM_001407585.1:c.5626delAinsGGATCC NP_001394514.1:p.Ile1876Glyfs frameshift NM_001407587.1:c.5626delAinsGGATCC NP_001394516.1:p.Ile1876Glyfs frameshift NM_001407590.1:c.5623delAinsGGATCC NP_001394519.1:p.Ile1875Glyfs frameshift NM_001407591.1:c.5623delAinsGGATCC NP_001394520.1:p.Ile1875Glyfs frameshift NM_001407593.1:c.5563delAinsGGATCC NP_001394522.1:p.Ile1855Glyfs frameshift NM_001407594.1:c.5563delAinsGGATCC NP_001394523.1:p.Ile1855Glyfs frameshift NM_001407596.1:c.5563delAinsGGATCC NP_001394525.1:p.Ile1855Glyfs frameshift NM_001407597.1:c.5563delAinsGGATCC NP_001394526.1:p.Ile1855Glyfs frameshift NM_001407598.1:c.5563delAinsGGATCC NP_001394527.1:p.Ile1855Glyfs frameshift NM_001407602.1:c.5563delAinsGGATCC NP_001394531.1:p.Ile1855Glyfs frameshift NM_001407603.1:c.5563delAinsGGATCC NP_001394532.1:p.Ile1855Glyfs frameshift NM_001407605.1:c.5563delAinsGGATCC NP_001394534.1:p.Ile1855Glyfs frameshift NM_001407610.1:c.5560delAinsGGATCC NP_001394539.1:p.Ile1854Glyfs frameshift NM_001407611.1:c.5560delAinsGGATCC NP_001394540.1:p.Ile1854Glyfs frameshift NM_001407612.1:c.5560delAinsGGATCC NP_001394541.1:p.Ile1854Glyfs frameshift NM_001407613.1:c.5560delAinsGGATCC NP_001394542.1:p.Ile1854Glyfs frameshift NM_001407614.1:c.5560delAinsGGATCC NP_001394543.1:p.Ile1854Glyfs frameshift NM_001407615.1:c.5560delAinsGGATCC NP_001394544.1:p.Ile1854Glyfs frameshift NM_001407616.1:c.5560delAinsGGATCC NP_001394545.1:p.Ile1854Glyfs frameshift NM_001407617.1:c.5560delAinsGGATCC NP_001394546.1:p.Ile1854Glyfs frameshift NM_001407618.1:c.5560delAinsGGATCC NP_001394547.1:p.Ile1854Glyfs frameshift NM_001407619.1:c.5560delAinsGGATCC NP_001394548.1:p.Ile1854Glyfs frameshift NM_001407620.1:c.5560delAinsGGATCC NP_001394549.1:p.Ile1854Glyfs frameshift NM_001407621.1:c.5560delAinsGGATCC NP_001394550.1:p.Ile1854Glyfs frameshift NM_001407622.1:c.5560delAinsGGATCC NP_001394551.1:p.Ile1854Glyfs frameshift NM_001407623.1:c.5560delAinsGGATCC NP_001394552.1:p.Ile1854Glyfs frameshift NM_001407624.1:c.5560delAinsGGATCC NP_001394553.1:p.Ile1854Glyfs frameshift NM_001407625.1:c.5560delAinsGGATCC NP_001394554.1:p.Ile1854Glyfs frameshift NM_001407626.1:c.5560delAinsGGATCC NP_001394555.1:p.Ile1854Glyfs frameshift NM_001407627.1:c.5557delAinsGGATCC NP_001394556.1:p.Ile1853Glyfs frameshift NM_001407628.1:c.5557delAinsGGATCC NP_001394557.1:p.Ile1853Glyfs frameshift NM_001407629.1:c.5557delAinsGGATCC NP_001394558.1:p.Ile1853Glyfs frameshift NM_001407630.1:c.5557delAinsGGATCC NP_001394559.1:p.Ile1853Glyfs frameshift NM_001407631.1:c.5557delAinsGGATCC NP_001394560.1:p.Ile1853Glyfs frameshift NM_001407632.1:c.5557delAinsGGATCC NP_001394561.1:p.Ile1853Glyfs frameshift NM_001407633.1:c.5557delAinsGGATCC NP_001394562.1:p.Ile1853Glyfs frameshift NM_001407634.1:c.5557delAinsGGATCC NP_001394563.1:p.Ile1853Glyfs frameshift NM_001407635.1:c.5557delAinsGGATCC NP_001394564.1:p.Ile1853Glyfs frameshift NM_001407636.1:c.5557delAinsGGATCC NP_001394565.1:p.Ile1853Glyfs frameshift NM_001407637.1:c.5557delAinsGGATCC NP_001394566.1:p.Ile1853Glyfs frameshift NM_001407638.1:c.5557delAinsGGATCC NP_001394567.1:p.Ile1853Glyfs frameshift NM_001407639.1:c.5557delAinsGGATCC NP_001394568.1:p.Ile1853Glyfs frameshift NM_001407640.1:c.5557delAinsGGATCC NP_001394569.1:p.Ile1853Glyfs frameshift NM_001407641.1:c.5557delAinsGGATCC NP_001394570.1:p.Ile1853Glyfs frameshift NM_001407642.1:c.5557delAinsGGATCC NP_001394571.1:p.Ile1853Glyfs frameshift NM_001407644.1:c.5554delAinsGGATCC NP_001394573.1:p.Ile1852Glyfs frameshift NM_001407645.1:c.5554delAinsGGATCC NP_001394574.1:p.Ile1852Glyfs frameshift NM_001407646.1:c.5551delAinsGGATCC NP_001394575.1:p.Ile1851Glyfs frameshift NM_001407647.1:c.5548delAinsGGATCC NP_001394576.1:p.Ile1850Glyfs frameshift NM_001407648.1:c.5506delAinsGGATCC NP_001394577.1:p.Ile1836Glyfs frameshift NM_001407649.1:c.5503delAinsGGATCC NP_001394578.1:p.Ile1835Glyfs frameshift NM_001407652.1:c.5485delAinsGGATCC NP_001394581.1:p.Ile1829Glyfs frameshift NM_001407653.1:c.5485delAinsGGATCC NP_001394582.1:p.Ile1829Glyfs frameshift NM_001407654.1:c.5485delAinsGGATCC NP_001394583.1:p.Ile1829Glyfs frameshift NM_001407655.1:c.5485delAinsGGATCC NP_001394584.1:p.Ile1829Glyfs frameshift NM_001407656.1:c.5482delAinsGGATCC NP_001394585.1:p.Ile1828Glyfs frameshift NM_001407657.1:c.5482delAinsGGATCC NP_001394586.1:p.Ile1828Glyfs frameshift NM_001407658.1:c.5482delAinsGGATCC NP_001394587.1:p.Ile1828Glyfs frameshift NM_001407659.1:c.5479delAinsGGATCC NP_001394588.1:p.Ile1827Glyfs frameshift NM_001407660.1:c.5479delAinsGGATCC NP_001394589.1:p.Ile1827Glyfs frameshift NM_001407661.1:c.5479delAinsGGATCC NP_001394590.1:p.Ile1827Glyfs frameshift NM_001407662.1:c.5479delAinsGGATCC NP_001394591.1:p.Ile1827Glyfs frameshift NM_001407663.1:c.5479delAinsGGATCC NP_001394592.1:p.Ile1827Glyfs frameshift NM_001407664.1:c.5440delAinsGGATCC NP_001394593.1:p.Ile1814Glyfs frameshift NM_001407665.1:c.5440delAinsGGATCC NP_001394594.1:p.Ile1814Glyfs frameshift NM_001407666.1:c.5440delAinsGGATCC NP_001394595.1:p.Ile1814Glyfs frameshift NM_001407667.1:c.5440delAinsGGATCC NP_001394596.1:p.Ile1814Glyfs frameshift NM_001407668.1:c.5440delAinsGGATCC NP_001394597.1:p.Ile1814Glyfs frameshift NM_001407669.1:c.5440delAinsGGATCC NP_001394598.1:p.Ile1814Glyfs frameshift NM_001407670.1:c.5437delAinsGGATCC NP_001394599.1:p.Ile1813Glyfs frameshift NM_001407671.1:c.5437delAinsGGATCC NP_001394600.1:p.Ile1813Glyfs frameshift NM_001407672.1:c.5437delAinsGGATCC NP_001394601.1:p.Ile1813Glyfs frameshift NM_001407673.1:c.5437delAinsGGATCC NP_001394602.1:p.Ile1813Glyfs frameshift NM_001407674.1:c.5437delAinsGGATCC NP_001394603.1:p.Ile1813Glyfs frameshift NM_001407675.1:c.5437delAinsGGATCC NP_001394604.1:p.Ile1813Glyfs frameshift NM_001407676.1:c.5437delAinsGGATCC NP_001394605.1:p.Ile1813Glyfs frameshift NM_001407677.1:c.5437delAinsGGATCC NP_001394606.1:p.Ile1813Glyfs frameshift NM_001407678.1:c.5437delAinsGGATCC NP_001394607.1:p.Ile1813Glyfs frameshift NM_001407679.1:c.5437delAinsGGATCC NP_001394608.1:p.Ile1813Glyfs frameshift NM_001407680.1:c.5437delAinsGGATCC NP_001394609.1:p.Ile1813Glyfs frameshift NM_001407681.1:c.5434delAinsGGATCC NP_001394610.1:p.Ile1812Glyfs frameshift NM_001407682.1:c.5434delAinsGGATCC NP_001394611.1:p.Ile1812Glyfs frameshift NM_001407683.1:c.5434delAinsGGATCC NP_001394612.1:p.Ile1812Glyfs frameshift NM_001407684.1:c.5434delAinsGGATCC NP_001394613.1:p.Ile1812Glyfs frameshift NM_001407685.1:c.5434delAinsGGATCC NP_001394614.1:p.Ile1812Glyfs frameshift NM_001407686.1:c.5434delAinsGGATCC NP_001394615.1:p.Ile1812Glyfs frameshift NM_001407687.1:c.5434delAinsGGATCC NP_001394616.1:p.Ile1812Glyfs frameshift NM_001407688.1:c.5434delAinsGGATCC NP_001394617.1:p.Ile1812Glyfs frameshift NM_001407689.1:c.5434delAinsGGATCC NP_001394618.1:p.Ile1812Glyfs frameshift NM_001407690.1:c.5431delAinsGGATCC NP_001394619.1:p.Ile1811Glyfs frameshift NM_001407691.1:c.5431delAinsGGATCC NP_001394620.1:p.Ile1811Glyfs frameshift NM_001407692.1:c.5422delAinsGGATCC NP_001394621.1:p.Ile1808Glyfs frameshift NM_001407694.1:c.5422delAinsGGATCC NP_001394623.1:p.Ile1808Glyfs frameshift NM_001407695.1:c.5422delAinsGGATCC NP_001394624.1:p.Ile1808Glyfs frameshift NM_001407696.1:c.5422delAinsGGATCC NP_001394625.1:p.Ile1808Glyfs frameshift NM_001407697.1:c.5422delAinsGGATCC NP_001394626.1:p.Ile1808Glyfs frameshift NM_001407698.1:c.5422delAinsGGATCC NP_001394627.1:p.Ile1808Glyfs frameshift NM_001407724.1:c.5422delAinsGGATCC NP_001394653.1:p.Ile1808Glyfs frameshift NM_001407725.1:c.5422delAinsGGATCC NP_001394654.1:p.Ile1808Glyfs frameshift NM_001407726.1:c.5422delAinsGGATCC NP_001394655.1:p.Ile1808Glyfs frameshift NM_001407727.1:c.5422delAinsGGATCC NP_001394656.1:p.Ile1808Glyfs frameshift NM_001407728.1:c.5422delAinsGGATCC NP_001394657.1:p.Ile1808Glyfs frameshift NM_001407729.1:c.5422delAinsGGATCC NP_001394658.1:p.Ile1808Glyfs frameshift NM_001407730.1:c.5422delAinsGGATCC NP_001394659.1:p.Ile1808Glyfs frameshift NM_001407731.1:c.5422delAinsGGATCC NP_001394660.1:p.Ile1808Glyfs frameshift NM_001407732.1:c.5419delAinsGGATCC NP_001394661.1:p.Ile1807Glyfs frameshift NM_001407733.1:c.5419delAinsGGATCC NP_001394662.1:p.Ile1807Glyfs frameshift NM_001407734.1:c.5419delAinsGGATCC NP_001394663.1:p.Ile1807Glyfs frameshift NM_001407735.1:c.5419delAinsGGATCC NP_001394664.1:p.Ile1807Glyfs frameshift NM_001407736.1:c.5419delAinsGGATCC NP_001394665.1:p.Ile1807Glyfs frameshift NM_001407737.1:c.5419delAinsGGATCC NP_001394666.1:p.Ile1807Glyfs frameshift NM_001407738.1:c.5419delAinsGGATCC NP_001394667.1:p.Ile1807Glyfs frameshift NM_001407739.1:c.5419delAinsGGATCC NP_001394668.1:p.Ile1807Glyfs frameshift NM_001407740.1:c.5419delAinsGGATCC NP_001394669.1:p.Ile1807Glyfs frameshift NM_001407741.1:c.5419delAinsGGATCC NP_001394670.1:p.Ile1807Glyfs frameshift NM_001407742.1:c.5419delAinsGGATCC NP_001394671.1:p.Ile1807Glyfs frameshift NM_001407743.1:c.5419delAinsGGATCC NP_001394672.1:p.Ile1807Glyfs frameshift NM_001407744.1:c.5419delAinsGGATCC NP_001394673.1:p.Ile1807Glyfs frameshift NM_001407745.1:c.5419delAinsGGATCC NP_001394674.1:p.Ile1807Glyfs frameshift NM_001407746.1:c.5419delAinsGGATCC NP_001394675.1:p.Ile1807Glyfs frameshift NM_001407747.1:c.5419delAinsGGATCC NP_001394676.1:p.Ile1807Glyfs frameshift NM_001407748.1:c.5419delAinsGGATCC NP_001394677.1:p.Ile1807Glyfs frameshift NM_001407749.1:c.5419delAinsGGATCC NP_001394678.1:p.Ile1807Glyfs frameshift NM_001407750.1:c.5419delAinsGGATCC NP_001394679.1:p.Ile1807Glyfs frameshift NM_001407751.1:c.5419delAinsGGATCC NP_001394680.1:p.Ile1807Glyfs frameshift NM_001407752.1:c.5419delAinsGGATCC NP_001394681.1:p.Ile1807Glyfs frameshift NM_001407838.1:c.5416delAinsGGATCC NP_001394767.1:p.Ile1806Glyfs frameshift NM_001407839.1:c.5416delAinsGGATCC NP_001394768.1:p.Ile1806Glyfs frameshift NM_001407841.1:c.5416delAinsGGATCC NP_001394770.1:p.Ile1806Glyfs frameshift NM_001407842.1:c.5416delAinsGGATCC NP_001394771.1:p.Ile1806Glyfs frameshift NM_001407843.1:c.5416delAinsGGATCC NP_001394772.1:p.Ile1806Glyfs frameshift NM_001407844.1:c.5416delAinsGGATCC NP_001394773.1:p.Ile1806Glyfs frameshift NM_001407845.1:c.5416delAinsGGATCC NP_001394774.1:p.Ile1806Glyfs frameshift NM_001407846.1:c.5416delAinsGGATCC NP_001394775.1:p.Ile1806Glyfs frameshift NM_001407847.1:c.5416delAinsGGATCC NP_001394776.1:p.Ile1806Glyfs frameshift NM_001407848.1:c.5416delAinsGGATCC NP_001394777.1:p.Ile1806Glyfs frameshift NM_001407849.1:c.5416delAinsGGATCC NP_001394778.1:p.Ile1806Glyfs frameshift NM_001407850.1:c.5416delAinsGGATCC NP_001394779.1:p.Ile1806Glyfs frameshift NM_001407851.1:c.5416delAinsGGATCC NP_001394780.1:p.Ile1806Glyfs frameshift NM_001407852.1:c.5416delAinsGGATCC NP_001394781.1:p.Ile1806Glyfs frameshift NM_001407853.1:c.5416delAinsGGATCC NP_001394782.1:p.Ile1806Glyfs frameshift NM_001407854.1:c.*77delAinsGGATCC NM_001407858.1:c.*77delAinsGGATCC NM_001407859.1:c.*77delAinsGGATCC NM_001407860.1:c.*77delAinsGGATCC NM_001407861.1:c.*77delAinsGGATCC NM_001407862.1:c.5362delAinsGGATCC NP_001394791.1:p.Ile1788Glyfs frameshift NM_001407863.1:c.5359delAinsGGATCC NP_001394792.1:p.Ile1787Glyfs frameshift NM_001407874.1:c.5356delAinsGGATCC NP_001394803.1:p.Ile1786Glyfs frameshift NM_001407875.1:c.5356delAinsGGATCC NP_001394804.1:p.Ile1786Glyfs frameshift NM_001407879.1:c.5353delAinsGGATCC NP_001394808.1:p.Ile1785Glyfs frameshift NM_001407881.1:c.5353delAinsGGATCC NP_001394810.1:p.Ile1785Glyfs frameshift NM_001407882.1:c.5353delAinsGGATCC NP_001394811.1:p.Ile1785Glyfs frameshift NM_001407884.1:c.5353delAinsGGATCC NP_001394813.1:p.Ile1785Glyfs frameshift NM_001407885.1:c.5353delAinsGGATCC NP_001394814.1:p.Ile1785Glyfs frameshift NM_001407886.1:c.5353delAinsGGATCC NP_001394815.1:p.Ile1785Glyfs frameshift NM_001407887.1:c.5353delAinsGGATCC NP_001394816.1:p.Ile1785Glyfs frameshift NM_001407889.1:c.5353delAinsGGATCC NP_001394818.1:p.Ile1785Glyfs frameshift NM_001407894.1:c.5350delAinsGGATCC NP_001394823.1:p.Ile1784Glyfs frameshift NM_001407895.1:c.5350delAinsGGATCC NP_001394824.1:p.Ile1784Glyfs frameshift NM_001407896.1:c.5350delAinsGGATCC NP_001394825.1:p.Ile1784Glyfs frameshift NM_001407897.1:c.5350delAinsGGATCC NP_001394826.1:p.Ile1784Glyfs frameshift NM_001407898.1:c.5350delAinsGGATCC NP_001394827.1:p.Ile1784Glyfs frameshift NM_001407899.1:c.5350delAinsGGATCC NP_001394828.1:p.Ile1784Glyfs frameshift NM_001407900.1:c.5350delAinsGGATCC NP_001394829.1:p.Ile1784Glyfs frameshift NM_001407902.1:c.5350delAinsGGATCC NP_001394831.1:p.Ile1784Glyfs frameshift NM_001407904.1:c.5350delAinsGGATCC NP_001394833.1:p.Ile1784Glyfs frameshift NM_001407906.1:c.5350delAinsGGATCC NP_001394835.1:p.Ile1784Glyfs frameshift NM_001407907.1:c.5350delAinsGGATCC NP_001394836.1:p.Ile1784Glyfs frameshift NM_001407908.1:c.5350delAinsGGATCC NP_001394837.1:p.Ile1784Glyfs frameshift NM_001407909.1:c.5350delAinsGGATCC NP_001394838.1:p.Ile1784Glyfs frameshift NM_001407910.1:c.5350delAinsGGATCC NP_001394839.1:p.Ile1784Glyfs frameshift NM_001407915.1:c.5347delAinsGGATCC NP_001394844.1:p.Ile1783Glyfs frameshift NM_001407916.1:c.5347delAinsGGATCC NP_001394845.1:p.Ile1783Glyfs frameshift NM_001407917.1:c.5347delAinsGGATCC NP_001394846.1:p.Ile1783Glyfs frameshift NM_001407918.1:c.5347delAinsGGATCC NP_001394847.1:p.Ile1783Glyfs frameshift NM_001407919.1:c.5311delAinsGGATCC NP_001394848.1:p.Ile1771Glyfs frameshift NM_001407920.1:c.5299delAinsGGATCC NP_001394849.1:p.Ile1767Glyfs frameshift NM_001407921.1:c.5299delAinsGGATCC NP_001394850.1:p.Ile1767Glyfs frameshift NM_001407922.1:c.5299delAinsGGATCC NP_001394851.1:p.Ile1767Glyfs frameshift NM_001407923.1:c.5299delAinsGGATCC NP_001394852.1:p.Ile1767Glyfs frameshift NM_001407924.1:c.5299delAinsGGATCC NP_001394853.1:p.Ile1767Glyfs frameshift NM_001407925.1:c.5299delAinsGGATCC NP_001394854.1:p.Ile1767Glyfs frameshift NM_001407926.1:c.5299delAinsGGATCC NP_001394855.1:p.Ile1767Glyfs frameshift NM_001407927.1:c.5296delAinsGGATCC NP_001394856.1:p.Ile1766Glyfs frameshift NM_001407928.1:c.5296delAinsGGATCC NP_001394857.1:p.Ile1766Glyfs frameshift NM_001407929.1:c.5296delAinsGGATCC NP_001394858.1:p.Ile1766Glyfs frameshift NM_001407930.1:c.5296delAinsGGATCC NP_001394859.1:p.Ile1766Glyfs frameshift NM_001407931.1:c.5296delAinsGGATCC NP_001394860.1:p.Ile1766Glyfs frameshift NM_001407932.1:c.5296delAinsGGATCC NP_001394861.1:p.Ile1766Glyfs frameshift NM_001407933.1:c.5296delAinsGGATCC NP_001394862.1:p.Ile1766Glyfs frameshift NM_001407934.1:c.5293delAinsGGATCC NP_001394863.1:p.Ile1765Glyfs frameshift NM_001407935.1:c.5293delAinsGGATCC NP_001394864.1:p.Ile1765Glyfs frameshift NM_001407936.1:c.5293delAinsGGATCC NP_001394865.1:p.Ile1765Glyfs frameshift NM_001407937.1:c.*77delAinsGGATCC NM_001407938.1:c.*77delAinsGGATCC NM_001407939.1:c.*77delAinsGGATCC NM_001407940.1:c.*77delAinsGGATCC NM_001407941.1:c.*77delAinsGGATCC NM_001407942.1:c.*77delAinsGGATCC NM_001407943.1:c.*77delAinsGGATCC NM_001407944.1:c.*77delAinsGGATCC NM_001407945.1:c.*77delAinsGGATCC NM_001407946.1:c.5230delAinsGGATCC NP_001394875.1:p.Ile1744Glyfs frameshift NM_001407947.1:c.5230delAinsGGATCC NP_001394876.1:p.Ile1744Glyfs frameshift NM_001407948.1:c.5230delAinsGGATCC NP_001394877.1:p.Ile1744Glyfs frameshift NM_001407949.1:c.5230delAinsGGATCC NP_001394878.1:p.Ile1744Glyfs frameshift NM_001407950.1:c.5227delAinsGGATCC NP_001394879.1:p.Ile1743Glyfs frameshift NM_001407951.1:c.5227delAinsGGATCC NP_001394880.1:p.Ile1743Glyfs frameshift NM_001407952.1:c.5227delAinsGGATCC NP_001394881.1:p.Ile1743Glyfs frameshift NM_001407953.1:c.5227delAinsGGATCC NP_001394882.1:p.Ile1743Glyfs frameshift NM_001407954.1:c.5227delAinsGGATCC NP_001394883.1:p.Ile1743Glyfs frameshift NM_001407955.1:c.5227delAinsGGATCC NP_001394884.1:p.Ile1743Glyfs frameshift NM_001407956.1:c.5224delAinsGGATCC NP_001394885.1:p.Ile1742Glyfs frameshift NM_001407957.1:c.5224delAinsGGATCC NP_001394886.1:p.Ile1742Glyfs frameshift NM_001407958.1:c.5224delAinsGGATCC NP_001394887.1:p.Ile1742Glyfs frameshift NM_001407959.1:c.5182delAinsGGATCC NP_001394888.1:p.Ile1728Glyfs frameshift NM_001407960.1:c.5179delAinsGGATCC NP_001394889.1:p.Ile1727Glyfs frameshift NM_001407962.1:c.5179delAinsGGATCC NP_001394891.1:p.Ile1727Glyfs frameshift NM_001407963.1:c.5176delAinsGGATCC NP_001394892.1:p.Ile1726Glyfs frameshift NM_001407964.1:c.5101delAinsGGATCC NP_001394893.1:p.Ile1701Glyfs frameshift NM_001407965.1:c.5056delAinsGGATCC NP_001394894.1:p.Ile1686Glyfs frameshift NM_001407966.1:c.4675delAinsGGATCC NP_001394895.1:p.Ile1559Glyfs frameshift NM_001407967.1:c.4672delAinsGGATCC NP_001394896.1:p.Ile1558Glyfs frameshift NM_001407968.1:c.2959delAinsGGATCC NP_001394897.1:p.Ile987Glyfs frameshift NM_001407969.1:c.2956delAinsGGATCC NP_001394898.1:p.Ile986Glyfs frameshift NM_001407970.1:c.2320delAinsGGATCC NP_001394899.1:p.Ile774Glyfs frameshift NM_001407971.1:c.2320delAinsGGATCC NP_001394900.1:p.Ile774Glyfs frameshift NM_001407972.1:c.2317delAinsGGATCC NP_001394901.1:p.Ile773Glyfs frameshift NM_001407973.1:c.2254delAinsGGATCC NP_001394902.1:p.Ile752Glyfs frameshift NM_001407974.1:c.2254delAinsGGATCC NP_001394903.1:p.Ile752Glyfs frameshift NM_001407975.1:c.2254delAinsGGATCC NP_001394904.1:p.Ile752Glyfs frameshift NM_001407976.1:c.2254delAinsGGATCC NP_001394905.1:p.Ile752Glyfs frameshift NM_001407977.1:c.2254delAinsGGATCC NP_001394906.1:p.Ile752Glyfs frameshift NM_001407978.1:c.2254delAinsGGATCC NP_001394907.1:p.Ile752Glyfs frameshift NM_001407979.1:c.2251delAinsGGATCC NP_001394908.1:p.Ile751Glyfs frameshift NM_001407980.1:c.2251delAinsGGATCC NP_001394909.1:p.Ile751Glyfs frameshift NM_001407981.1:c.2251delAinsGGATCC NP_001394910.1:p.Ile751Glyfs frameshift NM_001407982.1:c.2251delAinsGGATCC NP_001394911.1:p.Ile751Glyfs frameshift NM_001407983.1:c.2251delAinsGGATCC NP_001394912.1:p.Ile751Glyfs frameshift NM_001407984.1:c.2251delAinsGGATCC NP_001394913.1:p.Ile751Glyfs frameshift NM_001407985.1:c.2251delAinsGGATCC NP_001394914.1:p.Ile751Glyfs frameshift NM_001407986.1:c.2251delAinsGGATCC NP_001394915.1:p.Ile751Glyfs frameshift NM_001407990.1:c.2251delAinsGGATCC NP_001394919.1:p.Ile751Glyfs frameshift NM_001407991.1:c.2251delAinsGGATCC NP_001394920.1:p.Ile751Glyfs frameshift NM_001407992.1:c.2251delAinsGGATCC NP_001394921.1:p.Ile751Glyfs frameshift NM_001407993.1:c.2251delAinsGGATCC NP_001394922.1:p.Ile751Glyfs frameshift NM_001408392.1:c.2248delAinsGGATCC NP_001395321.1:p.Ile750Glyfs frameshift NM_001408396.1:c.2248delAinsGGATCC NP_001395325.1:p.Ile750Glyfs frameshift NM_001408397.1:c.2248delAinsGGATCC NP_001395326.1:p.Ile750Glyfs frameshift NM_001408398.1:c.2248delAinsGGATCC NP_001395327.1:p.Ile750Glyfs frameshift NM_001408399.1:c.2248delAinsGGATCC NP_001395328.1:p.Ile750Glyfs frameshift NM_001408400.1:c.2248delAinsGGATCC NP_001395329.1:p.Ile750Glyfs frameshift NM_001408401.1:c.2248delAinsGGATCC NP_001395330.1:p.Ile750Glyfs frameshift NM_001408402.1:c.2248delAinsGGATCC NP_001395331.1:p.Ile750Glyfs frameshift NM_001408403.1:c.2248delAinsGGATCC NP_001395332.1:p.Ile750Glyfs frameshift NM_001408404.1:c.2248delAinsGGATCC NP_001395333.1:p.Ile750Glyfs frameshift NM_001408406.1:c.2245delAinsGGATCC NP_001395335.1:p.Ile749Glyfs frameshift NM_001408407.1:c.2245delAinsGGATCC NP_001395336.1:p.Ile749Glyfs frameshift NM_001408408.1:c.2245delAinsGGATCC NP_001395337.1:p.Ile749Glyfs frameshift NM_001408409.1:c.2242delAinsGGATCC NP_001395338.1:p.Ile748Glyfs frameshift NM_001408410.1:c.2179delAinsGGATCC NP_001395339.1:p.Ile727Glyfs frameshift NM_001408411.1:c.2176delAinsGGATCC NP_001395340.1:p.Ile726Glyfs frameshift NM_001408412.1:c.2173delAinsGGATCC NP_001395341.1:p.Ile725Glyfs frameshift NM_001408413.1:c.2173delAinsGGATCC NP_001395342.1:p.Ile725Glyfs frameshift NM_001408414.1:c.2173delAinsGGATCC NP_001395343.1:p.Ile725Glyfs frameshift NM_001408415.1:c.2173delAinsGGATCC NP_001395344.1:p.Ile725Glyfs frameshift NM_001408416.1:c.2173delAinsGGATCC NP_001395345.1:p.Ile725Glyfs frameshift NM_001408418.1:c.2137delAinsGGATCC NP_001395347.1:p.Ile713Glyfs frameshift NM_001408419.1:c.2137delAinsGGATCC NP_001395348.1:p.Ile713Glyfs frameshift NM_001408420.1:c.2137delAinsGGATCC NP_001395349.1:p.Ile713Glyfs frameshift NM_001408421.1:c.2134delAinsGGATCC NP_001395350.1:p.Ile712Glyfs frameshift NM_001408422.1:c.2134delAinsGGATCC NP_001395351.1:p.Ile712Glyfs frameshift NM_001408423.1:c.2134delAinsGGATCC NP_001395352.1:p.Ile712Glyfs frameshift NM_001408424.1:c.2134delAinsGGATCC NP_001395353.1:p.Ile712Glyfs frameshift NM_001408425.1:c.2131delAinsGGATCC NP_001395354.1:p.Ile711Glyfs frameshift NM_001408426.1:c.2131delAinsGGATCC NP_001395355.1:p.Ile711Glyfs frameshift NM_001408427.1:c.2131delAinsGGATCC NP_001395356.1:p.Ile711Glyfs frameshift NM_001408428.1:c.2131delAinsGGATCC NP_001395357.1:p.Ile711Glyfs frameshift NM_001408429.1:c.2131delAinsGGATCC NP_001395358.1:p.Ile711Glyfs frameshift NM_001408430.1:c.2131delAinsGGATCC NP_001395359.1:p.Ile711Glyfs frameshift NM_001408431.1:c.2131delAinsGGATCC NP_001395360.1:p.Ile711Glyfs frameshift NM_001408432.1:c.2128delAinsGGATCC NP_001395361.1:p.Ile710Glyfs frameshift NM_001408433.1:c.2128delAinsGGATCC NP_001395362.1:p.Ile710Glyfs frameshift NM_001408434.1:c.2128delAinsGGATCC NP_001395363.1:p.Ile710Glyfs frameshift NM_001408435.1:c.2128delAinsGGATCC NP_001395364.1:p.Ile710Glyfs frameshift NM_001408436.1:c.2128delAinsGGATCC NP_001395365.1:p.Ile710Glyfs frameshift NM_001408437.1:c.2128delAinsGGATCC NP_001395366.1:p.Ile710Glyfs frameshift NM_001408438.1:c.2128delAinsGGATCC NP_001395367.1:p.Ile710Glyfs frameshift NM_001408439.1:c.2128delAinsGGATCC NP_001395368.1:p.Ile710Glyfs frameshift NM_001408440.1:c.2128delAinsGGATCC NP_001395369.1:p.Ile710Glyfs frameshift NM_001408441.1:c.2128delAinsGGATCC NP_001395370.1:p.Ile710Glyfs frameshift NM_001408442.1:c.2128delAinsGGATCC NP_001395371.1:p.Ile710Glyfs frameshift NM_001408443.1:c.2128delAinsGGATCC NP_001395372.1:p.Ile710Glyfs frameshift NM_001408444.1:c.2128delAinsGGATCC NP_001395373.1:p.Ile710Glyfs frameshift NM_001408445.1:c.2125delAinsGGATCC NP_001395374.1:p.Ile709Glyfs frameshift NM_001408446.1:c.2125delAinsGGATCC NP_001395375.1:p.Ile709Glyfs frameshift NM_001408447.1:c.2125delAinsGGATCC NP_001395376.1:p.Ile709Glyfs frameshift NM_001408448.1:c.2125delAinsGGATCC NP_001395377.1:p.Ile709Glyfs frameshift NM_001408450.1:c.2125delAinsGGATCC NP_001395379.1:p.Ile709Glyfs frameshift NM_001408451.1:c.2119delAinsGGATCC NP_001395380.1:p.Ile707Glyfs frameshift NM_001408452.1:c.2113delAinsGGATCC NP_001395381.1:p.Ile705Glyfs frameshift NM_001408453.1:c.2113delAinsGGATCC NP_001395382.1:p.Ile705Glyfs frameshift NM_001408454.1:c.2113delAinsGGATCC NP_001395383.1:p.Ile705Glyfs frameshift NM_001408455.1:c.2113delAinsGGATCC NP_001395384.1:p.Ile705Glyfs frameshift NM_001408456.1:c.2113delAinsGGATCC NP_001395385.1:p.Ile705Glyfs frameshift NM_001408457.1:c.2113delAinsGGATCC NP_001395386.1:p.Ile705Glyfs frameshift NM_001408458.1:c.2110delAinsGGATCC NP_001395387.1:p.Ile704Glyfs frameshift NM_001408459.1:c.2110delAinsGGATCC NP_001395388.1:p.Ile704Glyfs frameshift NM_001408460.1:c.2110delAinsGGATCC NP_001395389.1:p.Ile704Glyfs frameshift NM_001408461.1:c.2110delAinsGGATCC NP_001395390.1:p.Ile704Glyfs frameshift NM_001408462.1:c.2110delAinsGGATCC NP_001395391.1:p.Ile704Glyfs frameshift NM_001408463.1:c.2110delAinsGGATCC NP_001395392.1:p.Ile704Glyfs frameshift NM_001408464.1:c.2110delAinsGGATCC NP_001395393.1:p.Ile704Glyfs frameshift NM_001408465.1:c.2110delAinsGGATCC NP_001395394.1:p.Ile704Glyfs frameshift NM_001408466.1:c.2110delAinsGGATCC NP_001395395.1:p.Ile704Glyfs frameshift NM_001408467.1:c.2110delAinsGGATCC NP_001395396.1:p.Ile704Glyfs frameshift NM_001408468.1:c.2107delAinsGGATCC NP_001395397.1:p.Ile703Glyfs frameshift NM_001408469.1:c.2107delAinsGGATCC NP_001395398.1:p.Ile703Glyfs frameshift NM_001408470.1:c.2107delAinsGGATCC NP_001395399.1:p.Ile703Glyfs frameshift NM_001408472.1:c.*77delAinsGGATCC NM_001408473.1:c.*77delAinsGGATCC NM_001408474.1:c.2053delAinsGGATCC NP_001395403.1:p.Ile685Glyfs frameshift NM_001408475.1:c.2050delAinsGGATCC NP_001395404.1:p.Ile684Glyfs frameshift NM_001408476.1:c.2050delAinsGGATCC NP_001395405.1:p.Ile684Glyfs frameshift NM_001408478.1:c.2044delAinsGGATCC NP_001395407.1:p.Ile682Glyfs frameshift NM_001408479.1:c.2044delAinsGGATCC NP_001395408.1:p.Ile682Glyfs frameshift NM_001408480.1:c.2044delAinsGGATCC NP_001395409.1:p.Ile682Glyfs frameshift NM_001408481.1:c.2041delAinsGGATCC NP_001395410.1:p.Ile681Glyfs frameshift NM_001408482.1:c.2041delAinsGGATCC NP_001395411.1:p.Ile681Glyfs frameshift NM_001408483.1:c.2041delAinsGGATCC NP_001395412.1:p.Ile681Glyfs frameshift NM_001408484.1:c.2041delAinsGGATCC NP_001395413.1:p.Ile681Glyfs frameshift NM_001408485.1:c.2041delAinsGGATCC NP_001395414.1:p.Ile681Glyfs frameshift NM_001408489.1:c.2041delAinsGGATCC NP_001395418.1:p.Ile681Glyfs frameshift NM_001408490.1:c.2041delAinsGGATCC NP_001395419.1:p.Ile681Glyfs frameshift NM_001408491.1:c.2041delAinsGGATCC NP_001395420.1:p.Ile681Glyfs frameshift NM_001408492.1:c.2038delAinsGGATCC NP_001395421.1:p.Ile680Glyfs frameshift NM_001408493.1:c.2038delAinsGGATCC NP_001395422.1:p.Ile680Glyfs frameshift NM_001408494.1:c.2014delAinsGGATCC NP_001395423.1:p.Ile672Glyfs frameshift NM_001408495.1:c.2008delAinsGGATCC NP_001395424.1:p.Ile670Glyfs frameshift NM_001408496.1:c.1990delAinsGGATCC NP_001395425.1:p.Ile664Glyfs frameshift NM_001408497.1:c.1990delAinsGGATCC NP_001395426.1:p.Ile664Glyfs frameshift NM_001408498.1:c.1990delAinsGGATCC NP_001395427.1:p.Ile664Glyfs frameshift NM_001408499.1:c.1990delAinsGGATCC NP_001395428.1:p.Ile664Glyfs frameshift NM_001408500.1:c.1990delAinsGGATCC NP_001395429.1:p.Ile664Glyfs frameshift NM_001408501.1:c.1990delAinsGGATCC NP_001395430.1:p.Ile664Glyfs frameshift NM_001408502.1:c.1987delAinsGGATCC NP_001395431.1:p.Ile663Glyfs frameshift NM_001408503.1:c.1987delAinsGGATCC NP_001395432.1:p.Ile663Glyfs frameshift NM_001408504.1:c.1987delAinsGGATCC NP_001395433.1:p.Ile663Glyfs frameshift NM_001408505.1:c.1984delAinsGGATCC NP_001395434.1:p.Ile662Glyfs frameshift NM_001408506.1:c.1927delAinsGGATCC NP_001395435.1:p.Ile643Glyfs frameshift NM_001408507.1:c.1924delAinsGGATCC NP_001395436.1:p.Ile642Glyfs frameshift NM_001408508.1:c.1915delAinsGGATCC NP_001395437.1:p.Ile639Glyfs frameshift NM_001408509.1:c.1912delAinsGGATCC NP_001395438.1:p.Ile638Glyfs frameshift NM_001408510.1:c.1873delAinsGGATCC NP_001395439.1:p.Ile625Glyfs frameshift NM_001408511.1:c.1870delAinsGGATCC NP_001395440.1:p.Ile624Glyfs frameshift NM_001408512.1:c.1750delAinsGGATCC NP_001395441.1:p.Ile584Glyfs frameshift NM_001408513.1:c.1723delAinsGGATCC NP_001395442.1:p.Ile575Glyfs frameshift NM_001408514.1:c.1327delAinsGGATCC NP_001395443.1:p.Ile443Glyfs frameshift NM_007294.3:c.5563delinsGGATCC frameshift NM_007297.4:c.5422delinsGGATCC NP_009228.2:p.Ile1808fs frameshift NM_007298.4:c.2251delAinsGGATCC NP_009229.2:p.Ile751Glyfs frameshift NM_007299.4:c.*77delinsGGATCC 3 prime UTR NM_007300.4:c.5626delinsGGATCC NP_009231.2:p.Ile1876fs frameshift NM_007304.2:c.2251delAinsGGATCC NP_009235.2:p.Ile751Glyfs frameshift NR_027676.2:n.5740delinsGGATCC non-coding transcript variant NC_000017.11:g.43045707delinsGGATCC NC_000017.10:g.41197724delinsGGATCC NG_005905.2:g.172277delinsGGATCC LRG_292:g.172277delinsGGATCC LRG_292t1:c.5563delAinsGGATCC LRG_292p1:p.Ile1855Glyfs - Protein change
- I1808fs, I1855fs, I1876fs, I751fs
- Other names
- -
- Canonical SPDI
- NC_000017.11:43045706:T:GGATCC
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13044 | 14850 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 30, 2023 | RCV001024278.5 | |
| Likely pathogenic (1) |
criteria provided, single submitter
|
May 5, 2022 | RCV001241613.5 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Jan 30, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV001186263.5
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
The c.5563delAinsGGATCC variant, located in coding exon 22 of the BRCA1 gene, results from the deletion of one nucleotide and insertion of 6 nucleotides causing … (more)
The c.5563delAinsGGATCC variant, located in coding exon 22 of the BRCA1 gene, results from the deletion of one nucleotide and insertion of 6 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.I1855Gfs*69). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of BRCA1, is not expected to trigger nonsense-mediated mRNA decay, and results in the elongation of the protein by 58 amino acids. The exact functional impact of these inserted amino acids is unknown at this time. One functional study found that this alteration impaired BRCA1 transcriptional activation activity (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
|
|
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Likely pathogenic
(May 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001414641.3
First in ClinVar: Jul 16, 2020 Last updated: Feb 20, 2024 |
Comment:
This sequence change results in a frameshift in the BRCA1 gene (p.Ile1855Glyfs*69). While this is not anticipated to result in nonsense mediated decay, it is … (more)
This sequence change results in a frameshift in the BRCA1 gene (p.Ile1855Glyfs*69). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the BRCA1 protein and extend the protein by 68 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. The frameshift caused by this variant affects the C-terminal end of the BRCA1 protein, partially including the BRCT domain (residues 1646-1859), which is important for DNA repair activity (PMID: 11573086, 14576433, 15133503, 25652403). While a protein structural change is likely expected, functional studies have not been done to test whether or not this variant affects protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Comment:
Comment:
This sequence change results in a frameshift in the BRCA1 gene (p.Ile1855Glyfs*69). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the BRCA1 protein and extend the protein by 68 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. The frameshift caused by this variant affects the C-terminal end of the BRCA1 protein, partially including the BRCT domain (residues 1646-1859), which is important for DNA repair activity (PMID: 11573086, 14576433, 15133503, 25652403). While a protein structural change is likely expected, functional studies have not been done to test whether or not this variant affects protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
The c.5563delAinsGGATCC variant, located in coding exon 22 of the BRCA1 gene, results from the deletion of one nucleotide and insertion of 6 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.I1855Gfs*69). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of BRCA1, is not expected to trigger nonsense-mediated mRNA decay, and results in the elongation of the protein by 58 amino acids. The exact functional impact of these inserted amino acids is unknown at this time. One functional study found that this alteration impaired BRCA1 transcriptional activation activity (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Comment:
This sequence change results in a frameshift in the BRCA1 gene (p.Ile1855Glyfs*69). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 9 amino acid(s) of the BRCA1 protein and extend the protein by 68 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. The frameshift caused by this variant affects the C-terminal end of the BRCA1 protein, partially including the BRCT domain (residues 1646-1859), which is important for DNA repair activity (PMID: 11573086, 14576433, 15133503, 25652403). While a protein structural change is likely expected, functional studies have not been done to test whether or not this variant affects protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Functional variant analyses (FVAs) predict pathogenicity in the BRCA1 DNA double-strand break repair pathway. | Loke J | Human molecular genetics | 2015 | PMID: 25652403 |
| Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1. | Williams RS | Nature structural & molecular biology | 2004 | PMID: 15133503 |
| The BRCT domain is a phospho-protein binding domain. | Yu X | Science (New York, N.Y.) | 2003 | PMID: 14576433 |
| Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1. | Williams RS | Nature structural biology | 2001 | PMID: 11573086 |
Text-mined citations for rs483353103 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.