ClinVar

Description

ACMG Guidelines 2015 criteria PM1 Pathogenic Moderate: 2 functional domains – a nucleic acid-binding OB-fold (R2669-3184L aa), which functions as ssDNA binding and nucleic acid recognition site; and the Tower domain (M2831-2967T aa) with a major role in tumor suppression and DNA binding. Hot-spot has 29 non-VUS coding variants (16 pathogenic and 13 benign), pathogenicity = 55.2%, proximity score 6.295 > threshold 2.472. PM2 Pathogenic Moderate: Variant not found in GnomAD exomes. Variant not found in GnomAD genomes. PP3 Pathogenic Supporting: 7 pathogenic predictions from DANN, EIGEN, FATHMM-MKL, M-CAP, MutationTaster, PrimateAI and SIFT vs 2 benign predictions from MVP and REVEL. PP4 Pathogenic Supporting: Patient was diagnosd with breast cancer at the age 49 yo with strong family history of breast cancer. Therefore, this variant was classified as a Likely Pathogenic.