Submissions for variant NM_000059.4(BRCA2):c.430GTT[1] (p.Val145del)

dbSNP: rs80359442

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000202422	SCV000210543	likely benign	not provided	2019-07-29	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21218378, 19941162, 20104584, 29176636, 28758972)
Ambry Genetics	RCV000164811	SCV000215493	likely benign	Hereditary cancer-predisposing syndrome	2018-11-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080942	SCV000257480	likely benign	Hereditary breast ovarian cancer syndrome	2025-01-22	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164811	SCV000688869	benign	Hereditary cancer-predisposing syndrome	2016-11-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000417373	SCV000918856	likely benign	not specified	2021-04-05	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.433_435delGTT (p.Val145del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 250698 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.433_435delGTT has been reported in the literature in individuals affected with Breast and/or Ovarian Cancer (example, Borg_2010, Carney_2010, Alsop_2012, Arai_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Co-occurrences with other pathogenic variant(s) have been reported in the BIC database (BRCA1 c.5207T>C, p.Val1736Ala), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. They have cited the variant with a majority consensus leaning towards benign (n=1)/likely benign (n=3), and uncertain significance (n=1). Some submitters cite overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000202422	SCV001133792	uncertain significance	not provided	2024-09-07	criteria provided, single submitter	clinical testing	The BRCA2 c.433_435del (p.Val145del) variant has been reported in the published literature in individuals with breast cancer (PMID: 20104584 (2010), 34597585 (2021)) and ovarian cancer (PMID: 34326862 (2021)). This variant has also been identified in a reportedly healthy individual with family history of breast cancer (PMID: 21218378 (2010)). The frequency of this variant in the general population, 0.000039 (5/128808 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000202422	SCV002050261	likely benign	not provided	2024-01-12	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004803029	SCV005424241	benign	BRCA2-related cancer predisposition	2024-05-30	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031476	SCV000054081	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2012-06-11	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000031476	SCV000146839	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2002-05-29	no assertion criteria provided	clinical testing