Submissions for variant NM_007294.4(BRCA1):c.2028_2029del (p.Gly677fs)

dbSNP: rs397508931

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000660929	SCV000783167	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2017-12-15	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001526957	SCV001737730	likely pathogenic	Hereditary breast ovarian cancer syndrome	2021-06-07	criteria provided, single submitter	clinical testing	Variant summary: BRCA1 c.2028_2029delTG (p.Gly677SerfsX5) 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. The variant was absent in 251290 control chromosomes. c.2028_2029delTG has been reported in the literature in individuals affected with Hereditary Ovarian Cancer (example Sugino_2019 and no ascertainable primary evidence in Yoshihara_2011, Yoshihara_2020). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One expert panel (ENIGMA) has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577093	SCV000679526	not provided	Familial cancer of breast		no assertion provided	literature only