Submissions for variant NM_000059.4(BRCA2):c.5631del (p.Asn1877fs)

dbSNP: rs397507357

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031562	SCV000300909	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-09-08	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Ambry Genetics	RCV000166635	SCV000217439	pathogenic	Hereditary cancer-predisposing syndrome	2024-11-26	criteria provided, single submitter	clinical testing	The c.5631delC pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 5631, causing a translational frameshift with a predicted alternate stop codon (p.N1877Kfs*32). This alteration has been identified in individuals diagnosed with breast and/or ovarian cancer (Torres-Mejía G et al. Cancer Epidemiol. Biomarkers Prev. 2015 Mar;24(3):498-505; Millan Catalan O et al. Cancers (Basel), 2019 Aug;11:; Gallardo-Rincón D et al. Transl Oncol, 2020 Feb;13:212-220). Of note, this alteration is also designated as 5859delC in published literature. In addition to the clinical data presented in the literature, 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000505842	SCV000296614	pathogenic	not provided	2020-10-07	criteria provided, single submitter	clinical testing	This frameshift variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. The frequency of this variant in the general population, 0.000029 (1/34048 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In addition, it has been reported in individuals with breast cancer in the published literature (PMID: 31454914 (2019), 25371446 (2014)). Based on the available information, this variant is classified as pathogenic.
Counsyl	RCV000031562	SCV000488147	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-02-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000166635	SCV000688935	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 1/248274 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
GeneDx	RCV000505842	SCV000778883	pathogenic	not provided	2024-08-20	criteria provided, single submitter	clinical testing	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; Observed in individuals with a personal and/or family history of breast or ovarian cancer (PMID: 28888541, 31454914, 25371446); Not observed at 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 5859delC; This variant is associated with the following publications: (PMID: 26295337, 30720243, 30630528, 31454914, 34413315, 29922827, 28888541, 25371446)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001044806	SCV001208624	pathogenic	Hereditary breast ovarian cancer syndrome	2025-01-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn1877Lysfs*32) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs397507357, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 25371446). This variant is also known as c.5859delC. ClinVar contains an entry for this variant (Variation ID: 37981). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003473192	SCV004211936	pathogenic	Familial cancer of breast	2023-09-21	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004803048	SCV005424491	pathogenic	BRCA2-related cancer predisposition	2024-09-16	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with breast or ovarian cancer (PMID: 25371446, 31454914, 31869745; Color internal data). This variant has been identified in 1/248274 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Sharing Clinical Reports Project (SCRP)	RCV000031562	SCV000054167	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2010-09-14	no assertion criteria provided	clinical testing