ClinVar

Description

Variant summary: BRCA2 c.2998A>C (p.Ile1000Leu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250640 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2998A>C has been reported in the literature as a VUS in settings of BRCA1/2 sequencing in at-least one individual affected with Breast and/or Ovarian Cancer (example, Abu-Helalah_2020). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.