Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Lifecell International Pvt. |
RCV003991994 | SCV004809180 | likely pathogenic | Desbuquois dysplasia 1 | criteria provided, single submitter | clinical testing | The missense variant NM_138793.4(CANT1):c.836G>A (p.Gly279Asp) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. Although the variant is present at 0.0000% in gnomAD All, it has the flag "AC0" and may not represent the true population frequency. The p.Gly279Asp variant is novel (not in any individuals) in 1kG All. There is a moderate physicochemical difference between glycine and aspartic acid. The gene CANT1 contains 8 pathogenic missense variants, indicating that missense variants are a common mechanism of disease in this gene. The p.Gly279Asp missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 279 of CANT1 is conserved in all mammalian species. The nucleotide c.836 in CANT1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. Since the allele depth is less for the sample, sanger sequencing was performed to confirm the variant identifed in CVS sample. Sanger sequencing confirmed the variant in homozygous state in Fetal sample and parents were also found to be carriers for the reported variant. Based on the above evidence this variant has been classified aslikely pathogenic according to the ACMG guidelines. |