Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000509993 | SCV000608039 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-28 | criteria provided, single submitter | clinical testing | The p.A2951S variant (also known as c.8851G>T), located in coding exon 21 of the BRCA2 gene, results from a G to T substitution at nucleotide position 8851. The alanine at codon 2951 is replaced by serine, an amino acid with similar properties. This alteration was detected in 1/76 individuals of Armenian descent either with a personal and/or family history of cancer or breast. This patient was diagnosed with breast cancer at age 49 and had a family history of breast cancer in multiple relatives (Moradian MM et al. Hum Genome Var, 2021 Feb;8:9). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Center of Medical Genetics and Primary Health Care | RCV001005034 | SCV000987290 | likely pathogenic | Familial cancer of breast | 2020-04-08 | no assertion criteria provided | research | 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. |