Submissions for variant NM_000059.4(BRCA2):c.8944A>C (p.Lys2982Gln)

dbSNP: rs80359145

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000045662	SCV000073675	likely benign	Hereditary breast ovarian cancer syndrome	2025-01-21	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000708685	SCV000821948	uncertain significance	Hereditary cancer-predisposing syndrome	2018-08-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985613	SCV001133958	uncertain significance	not provided	2024-11-05	criteria provided, single submitter	clinical testing	The BRCA2 c.8944A>C (p.Lys2982Gln) variant has been reported in the published literature in individuals with a personal and/or family history of breast and/or ovarian cancer (PMIDs: 28364669 (2017), 28111427 (2017), 30982232 (2019), 31159747 (2019), 31907386 (2020), 33471991 (2021) see also LOVD (https://databases.lovd.nl/shared/)), as well as reportedly healthy individuals (PMIDs: 32467295 (2020), 33471991 (2021) see also LOVD (https://databases.lovd.nl/shared/)). The frequency of this variant in the general population, 0.000099 (3/30264 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Color Diagnostics, LLC DBA Color Health	RCV000708685	SCV001343954	likely benign	Hereditary cancer-predisposing syndrome	2021-06-10	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001818223	SCV002068229	uncertain significance	not specified	2017-12-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000708685	SCV002683945	uncertain significance	Hereditary cancer-predisposing syndrome	2024-09-12	criteria provided, single submitter	clinical testing	The p.K2982Q variant (also known as c.8944A>C), located in coding exon 21 of the BRCA2 gene, results from an A to C substitution at nucleotide position 8944. The lysine at codon 2982 is replaced by glutamine, an amino acid with similar properties. This alteration has been reported in a cohort of 745 Korean hereditary breast and ovarian cancer (HBOC) patients (HBOC) and was called a variant of uncertain significance (Park JS et al. Cancer Res Treat, 2017 Oct;49:1012-1021). This alteration has also been reported in 1/1197 individuals from Greece, Romania, and Turkey undergoing evaluation for inherited cancer predisposition (Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Baylor Genetics	RCV004566856	SCV005059047	uncertain significance	Familial cancer of breast	2024-02-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001818223	SCV005381662	uncertain significance	not specified	2024-08-01	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.8944A>C (p.Lys2982Gln) results in a conservative amino acid change located in the BRCA2, OB2 domain (IPR048262) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 248098 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8944A>C has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Kim_2020, Tsaousis_2019, Wang_2019). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported.The following publications have been ascertained in the context of this evaluation (PMID: 31907386, 31159747, 30982232). ClinVar contains an entry for this variant (Variation ID: 52705). Based on the evidence outlined above, the variant was classified as uncertain significance.
Breast Cancer Information Core (BIC) (BRCA2)	RCV000114017	SCV000147492	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2003-12-23	no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000114017	SCV004243842	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2020-03-02	no assertion criteria provided	clinical testing