ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.3640_3641GA[1] (p.Asn1215fs) (rs80357805)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215002 SCV000274331 pathogenic Hereditary cancer-predisposing syndrome 2016-03-09 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA1) RCV000112144 SCV000144821 pathogenic Breast-ovarian cancer, familial 1 2006-07-19 no assertion criteria provided clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000112144 SCV000325712 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112144 SCV000299985 pathogenic Breast-ovarian cancer, familial 1 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000657207 SCV000778933 pathogenic not provided 2018-09-24 criteria provided, single submitter clinical testing This deletion of two nucleotides in BRCA1 is denoted c.3642_3643delGA at the cDNA level and p.Asn1215LeufsX3 (N1215LfsX3) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAGA[delGA]ACTT. The deletion causes a frameshift which changes an Asparagine to a Leucine at codon 1215, and creates a premature stop codon at position 3 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA1 c.3642_3643delGA, also reported as BRCA1 3761_3762delGA using alternate nomenclature, has been reported in association with breast and ovarian cancer (Machackova 2001, Foretova 2004). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000779903 SCV000916805 pathogenic Hereditary breast and ovarian cancer syndrome 2018-09-26 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3642_3643delGA (p.Asn1215LeufsX3) 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. The variant was absent in 246070 control chromosomes (gnomAD). The variant, c.3642_3643delGA, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Machackova_2001, Machackova_2008). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
PreventionGenetics RCV000657207 SCV000806938 pathogenic not provided 2017-08-11 criteria provided, single submitter clinical testing

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