Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002281711 | SCV002571750 | likely pathogenic | Severe combined immunodeficiency disease | 2022-08-04 | criteria provided, single submitter | clinical testing | Variant summary: AK2 c.556C>T (p.Arg186Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251468 control chromosomes (gnomAD). c.556C>T has been reported in the literature in a homozygous and a compound heterozygous child (who carried exon 2 deletion in trans), both affected with reticular dysgenesis (Lagresle-Peyrou_2009, Hoenig_2017). In addition, the Arg186 amino acid is evolutionarily highly conserved, and occurs in an evolutionarily constrained region (Hoenig_2017, PMID 29358731). These data indicate that the variant is likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| OMIM | RCV000019920 | SCV000040218 | pathogenic | Reticular dysgenesis | 2009-01-01 | no assertion criteria provided | literature only |