ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7978T>G (p.Tyr2660Asp) (rs80359029)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480484 SCV000567102 pathogenic not provided 2015-07-09 criteria provided, single submitter clinical testing This pathogenic variant is denoted BRCA2 c.7978T>G at the cDNA level, p.Tyr2660Asp (Y2660D) at the protein level, and results in the change of a Tyrosine to an Aspartic Acid (TAT>GAT). Using alternate nomenclature, this variant has been previously published as BRCA2 8206T>G. BRCA2 Tyr2660Asp has been observed in multiple individuals with hereditary breast and ovarian cancer and has been reported to co-segregate with disease in affected family members (van der Hout 2006, Gomez-Garcia 2009, Mohammadi 2009). Cell based functional studies demonstrated impaired repair activity similar to other known pathogenic variants (Guidugli 2013). BRCA2 Tyr2660Asp was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Tyrosine and Aspartic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Tyr2660Asp occurs at a position that is conserved across species and is located within the DNA binding domain (Borg 2010). Multiple published computational models predict this variant to have a deleterious effect (Karchin 2008, Guidugli 2013, Moghadasi 2013) and in house In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the current evidence, we consider this variant to be pathogenic.
Color RCV000773273 SCV000906946 likely pathogenic Hereditary cancer-predisposing syndrome 2020-03-19 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077420 SCV000109218 likely pathogenic Breast-ovarian cancer, familial 2 2012-07-25 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077420 SCV000147240 uncertain significance Breast-ovarian cancer, familial 2 1999-04-05 no assertion criteria provided clinical testing

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