Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000826189 | SCV000967735 | pathogenic | Hereditary breast ovarian cancer syndrome | 2018-09-13 | criteria provided, single submitter | clinical testing | The p.Glu902AspfsX98 variant in BRCA1 has not been previously reported in indivi duals with BRCA1-associated cancer or in large population studies. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequen ce beginning at position 902 and leads to a premature termination codon 98 amino acids downstream. This alteration is then predicted to lead to a truncated or a bsent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in autosomal dominant hereditary breast and ovarian cancer (H BOC). Additionally, other loss of function variants located in the same exon as the p.Glu902AspfsX98 variant have been reported in individuals with HBOC (HGMD; Stenson 2017). In summary, this variant meets criteria to be classified as patho genic for HBOC in an autosomal dominant manner based on absence from controls an d its predicted impact on the protein. ACMG/AMP criteria applied: PM2, PVS1. |