U.S. flag

An official website of the United States government

NM_000059.4(BRCA2):c.5350_5351del (p.Asn1784fs) AND not provided

Germline classification:
Pathogenic (7 submissions)
Last evaluated:
Jan 4, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000074537.37

Allele description [Variation Report for NM_000059.4(BRCA2):c.5350_5351del (p.Asn1784fs)]

NM_000059.4(BRCA2):c.5350_5351del (p.Asn1784fs)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.4(BRCA2):c.5350_5351del (p.Asn1784fs)
HGVS:
  • NC_000013.10:g.32913837_32913838del
  • NC_000013.11:g.32339705_32339706del
  • NG_012772.3:g.29226_29227del
  • NM_000059.4:c.5350_5351delMANE SELECT
  • NP_000050.3:p.Asn1784fs
  • LRG_293:g.29226_29227del
  • NC_000013.10:g.32913837_32913838del
  • NC_000013.10:g.32913842_32913843del
  • NC_000013.10:g.32913842_32913843del
  • NC_000013.10:g.32913842_32913843delAA
  • NM_000059.3:c.5350_5351delAA
  • NM_000059.4:c.5350_5351del
  • U43746.1:n.5578_5579delAA
  • p.Asn1784Hisfs*2
  • p.Asn1784HisfsX2
  • p.Asn1784fs
  • p.N1784HFS*2
  • p.N1784HfsX2
Nucleotide change:
5578delAA
Links:
Breast Cancer Information Core (BIC) (BRCA2): 5578&base_change=del AA; dbSNP: rs80359507
NCBI 1000 Genomes Browser:
rs80359507
Molecular consequence:
  • NM_000059.4:c.5350_5351del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000108622GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Pathogenic
(Jun 24, 2020)
germlineclinical testing

Citation Link,

SCV000296699Quest Diagnostics Nichols Institute San Juan Capistrano
criteria provided, single submitter

(Quest Diagnostics criteria)
Pathogenic
(Jul 19, 2023)
unknownclinical testing

PubMed (13)
[See all records that cite these PMIDs]

SCV000778684Mayo Clinic Laboratories, Mayo Clinic
no assertion criteria provided
Pathogenic
(Dec 12, 2017)
unknownclinical testing

SCV000883477ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)
Pathogenic
(Aug 27, 2020)
germlineclinical testing

Citation Link,

SCV001447454Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Oct 23, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002024787Revvity Omics, Revvity
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Jan 4, 2024)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002037534Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Pathogenicgermlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot provided1not providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The spectrum of genetic variants in hereditary pancreatic cancer includes Fanconi anemia genes.

Slavin TP, Neuhausen SL, Nehoray B, Niell-Swiller M, Solomon I, Rybak C, Blazer K, Adamson A, Yang K, Sand S, Guerrero-Llamas N, Castillo D, Herzog J, Wu X, Tao S, Raja S, Chung V, Singh G, Nadesan S, Brown S, Cruz-Correa M, Petersen GM, et al.

Fam Cancer. 2018 Apr;17(2):235-245. doi: 10.1007/s10689-017-0019-5.

PubMed [citation]
PMID:
28687971
PMCID:
PMC5758436

Insights into BRCA Cancer Predisposition from Integrated Germline and Somatic Analyses in 7632 Cancers.

Yost S, Ruark E, Alexandrov LB, Rahman N.

JNCI Cancer Spectr. 2019 Jun;3(2):pkz028. doi: 10.1093/jncics/pkz028.

PubMed [citation]
PMID:
31360904
PMCID:
PMC6649772
See all PubMed Citations (14)

Details of each submission

From GeneDx, SCV000108622.15

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 5578delAA; This variant is associated with the following publications: (PMID: 23569316, 22006311, 23633455, 24504028, 17148771, 8988179, 9150172, 21233401, 11597388, 21324516, 26681312, 17688236, 16683254, 23725378, 21305653, 28008555, 27836010, 24094589, 29371908, 29084914, 28687971, 30720243, 30322717, 26689913, 31447099, 32853339, 32719484, 32338768, 30787465, 33087929, 31360904)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000296699.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (13)

Description

The BRCA2 c.5350_5351del (p.Asn1784Hisfs*2) variant (also known as 5578delAA and 5573delAA) alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant has been reported in the published literature in individuals with ovarian cancer (PMID: 21324516 (2011), 22006311 (2011), 23633455 (2013), 24504028 (2014)), breast cancer (PMID: 28008555 (2017), 31360904 (2019)), prostate cancer (PMID: 28687971 (2018), 32338768 (2020)), and pancreatic cancer (PMID: 29922827 (2018)). The frequency of this variant in the general population, 0.000032 (1/31198 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV000778684.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000883477.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The BRCA2 c.5350_5351delAA; p.Asn1784fs variant (rs80359507) has been identified in multiple individuals diagnosed with ovarian, fallopian tube or peritoneal cancer (Gayther 1997, Walsh 2011, Zhang 2011, Cunningham 2014). It is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 37959) and observed in only 1/30754 alleles in the Genome Aggregation Database. This variant causes a frameshift by deleting 2 nucleotides, so is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on the above information, this variant is considered pathogenic. References: Cunningham J et al. Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. Sci Rep. 2014. 4:4026. Gayther S et al. Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nat Genet. 1997. 15(1):103-5. Walsh T et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing.Proc Natl Acad Sci U S A. 2011. 108(44):18032-7. Zhang S et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer.Gynecol Oncol. 2011. 121(2):353-7.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001447454.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot providednot providednot providednot providednot provided

From Revvity Omics, Revvity, SCV002024787.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV002037534.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024