ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4779A>C (p.Glu1593Asp) (rs80358703)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113341 SCV001161663 benign Breast-ovarian cancer, familial 2 2019-06-18 reviewed by expert panel curation Variant allele has low bioinformatic likelihood to encode a missense alteration affecting protein function (Missense prior probability 0.02;, AND low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02;, AND minor allele frequency 0.00298 (South Asian), derived from gnomAD v2.1.1 non-cancer (2019-05-13).
Invitae RCV001082952 SCV000072504 benign Hereditary breast and ovarian cancer syndrome 2020-11-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129760 SCV000184567 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: 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.
GeneDx RCV000034442 SCV000210609 likely benign not provided 2020-03-23 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24728327, 17503080, 28918466, 28222693, 10923033, 22752604, 22703879, 26469044, 12442273, 27181684, 19656415)
Color Health, Inc RCV000129760 SCV000910667 benign Hereditary cancer-predisposing syndrome 2016-09-26 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001642543 SCV001854807 likely benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034442 SCV000043210 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
ITMI RCV000120321 SCV000084473 not provided not specified 2013-09-19 no assertion provided reference population
Breast Cancer Information Core (BIC) (BRCA2) RCV000113341 SCV000146480 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000113341 SCV000297529 benign Breast-ovarian cancer, familial 2 2010-09-13 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353910 SCV000591926 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Glu1593Asp variant was identified in 5 of 222 proband chromosomes (frequency: 0.023) from individuals with breast or ovarian cancer and was absent in 88 control chromosomes from these studies (Soumittra 2009, Saxena 2002). The variant was also identified in dbSNP (ID: rs80358703) “With allele of Uncertain significance”, LOVD, and the BIC database (3X with unknown clinical importance). This residue is conserved in mammals but not lower organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM) do not suggest a high likelihood of impact to the protein. In addition, Myriad classifies this variant as a polymorphism (personal communication). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.

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