Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000011453 | SCV000967591 | pathogenic | Osteopathia striata with cranial sclerosis | 2018-04-21 | criteria provided, single submitter | clinical testing | The p.Arg353X variant in AMER1 has been reported in 4 individuals with osteopath ia striata-cranial sclerosis (OSCS), occurring de novo in 2 individuals and segr egating with disease in an affected family member in 2 families (Jenkins 2009, Z icari 2012, Fradin 2017). The variant was not reported in large population datab ases, but has been reported in the COSMIC database as a somatic variant that was detected in two colorectal adenocarcinoma samples (Mutation ID: COSM6495573; ht tp://cancer.sanger.ac.uk/cosmic/). However, germline p.Arg353X variants in OSCS patients have not been associated with an increased risk of cancer (Jenkins 2009 , Zicari 2012, Fradin 2017). This nonsense variant leads to a premature terminat ion codon at position 353, and is predicted to result in a truncated protein (Je nkens 2009). Loss of function of AMER1 due to truncating germline variants is an established disease mechanism for OSCS. In summary, this variant meets criteria to be classified as pathogenic for OSCS in an X-linked dominant manner. ACMG/AM P Criteria applied: PM6_Strong; PM2; PM4; PS4_Moderate; PP4. |
Women's and Children's Health, |
RCV000011453 | SCV001426759 | pathogenic | Osteopathia striata with cranial sclerosis | criteria provided, single submitter | provider interpretation | ||
DASA | RCV000011453 | SCV002061240 | pathogenic | Osteopathia striata with cranial sclerosis | 2022-01-05 | criteria provided, single submitter | clinical testing | The c.1057C>T;p.(Arg353*) variant creates a premature translational stop signal in the AMER1 gene. It is expected to result in an absent or disrupted protein product -PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant(ClinVar ID: 10707; OMIM: 300647.0004; PMID: 19079258; 22716240; 27369646) - PS4. This variant is not present in population databases (rs137852216, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. The variant was assumed de novo, but without confirmation of paternity and maternity (PMID: 19079258, 27369646) - PM6. The variant co-segregated with disease in multiple affected family members (PMID: 22716240) - PP1. In summary, the currently available evidence indicates that the variant is pathogenic. |
Gene |
RCV002266900 | SCV002549244 | pathogenic | not provided | 2022-07-14 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 783 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32879452, 22716240, 27369646, 33504798, 19079258) |
OMIM | RCV000011453 | SCV000031685 | pathogenic | Osteopathia striata with cranial sclerosis | 2009-01-01 | no assertion criteria provided | literature only |