Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Pediatric Genomics Discovery Program, |
RCV001352889 | SCV001501146 | likely pathogenic | Ataxia-telangiectasia syndrome | 2021-03-10 | criteria provided, single submitter | research | The c.8708C>T, p.Pro2903Leu variant in ATM is absent in a large population database with over 250,000 alleles reported (gnomAD). Multiple in silico analyses (e.g. SIFT, PolyPhen, FATHMM, MetaSVM) predicted that the missense change p.Pro2903Leu has a deleterious effect with CADD score=34 or REVEL pathogenicity score=0.887. It was identified in a large family affected with adolescent-onset ataxia in trans with a known pathogenic ATM variant, segregating perfectly for recessive inheritance. Telangiectasias and cancers are not known in this family. These criteria suggest sufficient evidence to report this variant as likely pathogenic. |