The pathogenic role of the BRCA2 c.7847C>T (p.Ser2616Phe) variant in breast and ovarian cancer predisposition.
BRCA2 gene
genetic testing
hereditary breast and ovarian cancer syndrome
mutation
pedigree
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
revised:
08
03
2023
received:
24
10
2022
accepted:
22
03
2023
medline:
7
7
2023
pubmed:
18
4
2023
entrez:
17
4
2023
Statut:
ppublish
Résumé
Substantial numbers of variants of unknown significance (VUSs) have been identified in BRCA1/2 through genetic testing, which poses a significant clinical challenge because the contribution of these VUSs to cancer predisposition has not yet been determined. Here, we report 10 Japanese patients from seven families with breast or ovarian cancer harboring the BRCA2 c.7847C>T (p.Ser2616Phe) variant that was interpreted as a VUS. This variant recurs only in families from Japan and has not been reported in the global general population databases. A Japanese patient with Fanconi anemia with compound heterozygous variants c.7847C>T (p.Ser2616Phe) and c.475+1G>A in BRCA2 was reported. In silico predictions and quantitative cosegregation analysis suggest a high probability of pathogenicity. The clinical features of the variant carriers were not specific to, but were consistent with, those of patients with hereditary breast and ovarian cancer. A validated functional assay, called the mixed-all-nominated-in-one-BRCA (MANO-B) method and the accurate BRCA companion diagnostic (ABCD) test, demonstrated the deleterious effects of the variant. Altogether, following the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines, this variant satisfied the "PS3," "PM2," "PM3," and "PP3" criteria. We thus conclude that the BRCA2 c.7847C>T (p.Ser2616Phe) variant is a "likely pathogenic" variant that is specifically observed in the Japanese population, leading to a breast and ovarian cancer predisposition.
Identifiants
pubmed: 37067535
doi: 10.1111/cas.15799
pmc: PMC10323079
doi:
Substances chimiques
BRCA2 protein, human
0
BRCA2 Protein
0
BRCA1 protein, human
0
BRCA1 Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2993-3002Subventions
Organisme : Japan Agency for Medical Research and Development
ID : JP22ck0106536
Organisme : Japan Agency for Medical Research and Development
ID : JP22kk0305018
Organisme : Japan Society for the Promotion of Science
ID : 19H03628
Organisme : Japan Society for the Promotion of Science
ID : 20K19082
Organisme : Japan Society for the Promotion of Science
ID : 21K19751
Informations de copyright
© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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