The c.676_677delAA pathogenic mutation, located in coding exon 6 of the PMS2 gene, results from a deletion of two nucleotides at nucleotide positions 676 to 677, causing a translational frameshift with a predicted alternate stop codon (p.N226Yfs*22). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
ClinVar Genomic variation as it relates to human health
NM_000535.7(PMS2):c.676_677del (p.Asn226fs)
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.
(1)
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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.
Pathogenic
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000535.7(PMS2):c.676_677del (p.Asn226fs)
Variation ID: 3232033 Accession: VCV003232033.1
- Type and length
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Deletion, 2 bp
- Location
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Cytogenetic: 7p22.1 7: 5999136-5999137 (GRCh38) [ NCBI UCSC ] 7: 6038767-6038768 (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 May 1, 2024 May 1, 2024 Nov 28, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000535.7:c.676_677del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000526.2:p.Asn226fs frameshift NM_000535.5:c.676_677delAA frameshift NM_001018040.1:c.269_270delAA NP_001018050.1:p.Asn91Tyrfs frameshift NM_001322003.2:c.271_272del NP_001308932.1:p.Asn91fs frameshift NM_001322004.2:c.271_272del NP_001308933.1:p.Asn91fs frameshift NM_001322005.2:c.271_272del NP_001308934.1:p.Asn91fs frameshift NM_001322006.2:c.676_677del NP_001308935.1:p.Asn226fs frameshift NM_001322007.2:c.358_359del NP_001308936.1:p.Asn120fs frameshift NM_001322008.2:c.358_359del NP_001308937.1:p.Asn120fs frameshift NM_001322009.2:c.271_272del NP_001308938.1:p.Asn91fs frameshift NM_001322010.2:c.271_272del NP_001308939.1:p.Asn91fs frameshift NM_001322011.2:c.-258_-257del 5 prime UTR NM_001322012.2:c.-258_-257del 5 prime UTR NM_001322013.2:c.133-1714_133-1713del intron variant NM_001322014.2:c.676_677del NP_001308943.1:p.Asn226fs frameshift NM_001322015.2:c.367_368del NP_001308944.1:p.Asn123fs frameshift NM_001406866.1:c.862_863del NP_001393795.1:p.Asn288fs frameshift NM_001406868.1:c.700_701del NP_001393797.1:p.Asn234fs frameshift NM_001406869.1:c.597+79_597+80del intron variant NM_001406870.1:c.676_677del NP_001393799.1:p.Asn226fs frameshift NM_001406871.1:c.676_677del NP_001393800.1:p.Asn226fs frameshift NM_001406872.1:c.676_677del NP_001393801.1:p.Asn226fs frameshift NM_001406873.1:c.676_677del NP_001393802.1:p.Asn226fs frameshift NM_001406874.1:c.538-1714_538-1713del intron variant NM_001406875.1:c.367_368del NP_001393804.1:p.Asn123fs frameshift NM_001406876.1:c.358_359del NP_001393805.1:p.Asn120fs frameshift NM_001406877.1:c.367_368del NP_001393806.1:p.Asn123fs frameshift NM_001406878.1:c.367_368del NP_001393807.1:p.Asn123fs frameshift NM_001406879.1:c.367_368del NP_001393808.1:p.Asn123fs frameshift NM_001406880.1:c.367_368del NP_001393809.1:p.Asn123fs frameshift NM_001406881.1:c.367_368del NP_001393810.1:p.Asn123fs frameshift NM_001406882.1:c.367_368del NP_001393811.1:p.Asn123fs frameshift NM_001406883.1:c.358_359del NP_001393812.1:p.Asn120fs frameshift NM_001406884.1:c.538-1714_538-1713del intron variant NM_001406885.1:c.340_341del NP_001393814.1:p.Asn114fs frameshift NM_001406886.1:c.537+3316_537+3317del intron variant NM_001406887.1:c.271_272del NP_001393816.1:p.Asn91fs frameshift NM_001406888.1:c.271_272del NP_001393817.1:p.Asn91fs frameshift NM_001406889.1:c.271_272del NP_001393818.1:p.Asn91fs frameshift NM_001406890.1:c.271_272del NP_001393819.1:p.Asn91fs frameshift NM_001406891.1:c.271_272del NP_001393820.1:p.Asn91fs frameshift NM_001406892.1:c.271_272del NP_001393821.1:p.Asn91fs frameshift NM_001406893.1:c.271_272del NP_001393822.1:p.Asn91fs frameshift NM_001406894.1:c.271_272del NP_001393823.1:p.Asn91fs frameshift NM_001406895.1:c.271_272del NP_001393824.1:p.Asn91fs frameshift NM_001406896.1:c.271_272del NP_001393825.1:p.Asn91fs frameshift NM_001406897.1:c.271_272del NP_001393826.1:p.Asn91fs frameshift NM_001406898.1:c.271_272del NP_001393827.1:p.Asn91fs frameshift NM_001406899.1:c.271_272del NP_001393828.1:p.Asn91fs frameshift NM_001406900.1:c.367_368del NP_001393829.1:p.Asn123fs frameshift NM_001406901.1:c.358_359del NP_001393830.1:p.Asn120fs frameshift NM_001406902.1:c.358_359del NP_001393831.1:p.Asn120fs frameshift NM_001406903.1:c.358_359del NP_001393832.1:p.Asn120fs frameshift NM_001406904.1:c.192+79_192+80del intron variant NM_001406905.1:c.192+79_192+80del intron variant NM_001406906.1:c.271_272del NP_001393835.1:p.Asn91fs frameshift NM_001406907.1:c.271_272del NP_001393836.1:p.Asn91fs frameshift NM_001406908.1:c.271_272del NP_001393837.1:p.Asn91fs frameshift NM_001406909.1:c.133-1714_133-1713del intron variant NM_001406910.1:c.271_272del NP_001393839.1:p.Asn91fs frameshift NM_001406911.1:c.132+3316_132+3317del intron variant NM_001406912.1:c.676_677del NP_001393841.1:p.Asn226fs frameshift NR_003085.2:n.756_757delAA NR_136154.1:n.763_764del non-coding transcript variant NC_000007.14:g.5999138_5999139del NC_000007.13:g.6038769_6038770del NG_008466.1:g.14970_14971del LRG_161:g.14970_14971del LRG_161t1:c.674_675del LRG_161p1:p.Asn226Tyrfs - Protein change
- N114fs, N120fs, N123fs, N226fs, N234fs, N288fs, N91fs
- Other names
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- Canonical SPDI
- NC_000007.14:5999135:TTTT:TT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- 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 | ||
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| 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. |
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| PMS2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
5241 | 5343 | |
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. |
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| Pathogenic (1) |
criteria provided, single submitter
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Nov 28, 2023 | RCV004518748.1 |
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. |
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Pathogenic
(Nov 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV005036082.1
First in ClinVar: May 01, 2024 Last updated: May 01, 2024 |
Comment:
The c.676_677delAA pathogenic mutation, located in coding exon 6 of the PMS2 gene, results from a deletion of two nucleotides at nucleotide positions 676 to … (more)
The c.676_677delAA pathogenic mutation, located in coding exon 6 of the PMS2 gene, results from a deletion of two nucleotides at nucleotide positions 676 to 677, causing a translational frameshift with a predicted alternate stop codon (p.N226Yfs*22). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
|
Comment:
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.676_677delAA pathogenic mutation, located in coding exon 6 of the PMS2 gene, results from a deletion of two nucleotides at nucleotide positions 676 to 677, causing a translational frameshift with a predicted alternate stop codon (p.N226Yfs*22). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 08, 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.