Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000677225 | SCV002198877 | uncertain significance | Ataxia-telangiectasia syndrome | 2021-08-28 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATM protein function. ClinVar contains an entry for this variant (Variation ID: 559541). This missense change has been observed in individual(s) with clinical features of ataxia-telangiectasia (PMID: 30888062). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with serine at codon 2300 of the ATM protein (p.Trp2300Ser). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and serine. |
| 3billion | RCV000677225 | SCV002521509 | likely pathogenic | Ataxia-telangiectasia syndrome | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.85; 3Cnet: 0.95). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with ATM related disorder (ClinVar ID: VCV000559541 / PMID: 30888062). The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (PMID: 30888062). A different missense change at the same codon (p.Trp2300Gly) has been reported to be associated with ATM related disorder (PMID: 33098801). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| HUSP Clinical Genetics Laboratory, |
RCV000677225 | SCV000788257 | likely pathogenic | Ataxia-telangiectasia syndrome | 2018-07-26 | no assertion criteria provided | clinical testing | This variant (NM_000051.3:c.6899G>C) is seen in compound heterozygosity with the variant NG_009830.1(NM_000051.3):c.(2466+1_2467-1)_(8850+1_8851-1)dup in the affected child. |