Submissions for variant NM_000465.4(BARD1):c.623del (p.Lys208fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV003335652	SCV004044127	pathogenic	Familial cancer of breast	2023-05-19	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
GeneDx	RCV003443205	SCV004168222	likely pathogenic	not provided	2023-05-23	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30458888)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479516	SCV004222909	pathogenic	Malignant tumor of breast	2023-11-20	criteria provided, single submitter	clinical testing	Variant summary: BARD1 c.623delA (p.Lys208ArgfsX4) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant was absent in 230912 control chromosomes. To our knowledge, no occurrence of c.623delA in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.