Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| 3billion | RCV001253810 | SCV005905127 | likely pathogenic | Optic atrophy 12 | 2024-04-19 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v4.0.0 dataset. Predicted Consequence/Location: Missense variant Functional studies provide moderate evidence of the variant having a damaging effect on the gene or gene product (PMID: 32600459). In silico tool predictions suggest damaging effect of the variant on gene or gene product [REVEL: 0.91 (>=0.6, sensitivity 0.68 and specificity 0.92); 3Cnet: 0.42 (>=0.6, sensitivity 0.72 and precision 0.9)]. Same nucleotide change resulting in same amino acid change has been previously reported to be associated with AFG3L2 related disorder (ClinVar ID: VCV000976488 /PMID: 32548275).The variant has been observed in at least two similarly affected unrelated individuals (PMID: 32548275, 32600459). The variant has been reported to co-segregate with the disease in at least 5 similarly affected relatives/individuals in the same family or similarly affected unrelated families (PMID: 32600459). A different missense change at the same codon (p.Gly337Arg) has been reported to be associated with AFG3L2 related disorder (PMID: 32548275). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| OMIM | RCV001253810 | SCV001429683 | pathogenic | Optic atrophy 12 | 2020-08-14 | no assertion criteria provided | literature only |