Submissions for variant NM_000059.4(BRCA2):c.632-1dup

dbSNP: rs1566220586

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000779945	SCV000916890	likely pathogenic	Hereditary breast ovarian cancer syndrome	2018-03-20	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.632-1dupG (p.Val211GlyfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Val220fsX4 and p.Ser234fsX7). Several computational tools predict a significant impact on normal splicing: Four predict the variant creates a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 238130 control chromosomes. To our knowledge, no occurrence of c.632-1dupG in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.