Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gemeinschaftspraxis fuer Humangenetik Dresden | RCV002052435 | SCV002319224 | likely pathogenic | Fibrous dysplasia of jaw | 2021-12-11 | no assertion criteria provided | clinical testing | The Gly420Ala is not reported in HGMD 2021.3, gnomAD (v2.1.1), dbSNP (v151) or LOVD. On same position the pathogenic mutations Gly420Arg and Gly420Glu for the phenotype cherubism are known. In functional studies for the mutation p.Gly420Glu is shown, that it is inside an eight aminoacid motif, which is essential for recognition of SH3BP by tankyrase. Most detected mutations lay inside this motifs RSPPDGQS (AA 415-422). Multiple lines of computational evidence support a deleterious effect on the gene (AGVGD, SIFT, MutationTaster2021, Polyphen-2). In summary, the Gly420Ala variant meets our criteria to be classified as likely pathogenic. ACMG: PM1, PM2, PM5, PP3 (ACMG Guidelines, 2015) |