Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Lifecell International Pvt. |
RCV001542740 | SCV003923321 | likely pathogenic | Mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type) | criteria provided, single submitter | clinical testing | "A Homozygote Intron, Splice site donor, c.*3_*5+1delTAAG in Exon 28 of the OPA1 gene that results in the amino acid substitution was identified. The observed variant has a minor allele frequency of 0.00003% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Likely Pathogenic (Variation ID: 1184587). Based on the above evidence this variant has been classified as Likely Pathogenic according to the ACMG guidelines. Mitochondrial DNA depletion syndrome-14 (MTDPS14) is caused by homozygous mutation in the OPA1 gene on chromosome 3q29. Clinical features may include hypotonia and peripheral hypertonia with opisthotonic posturing from birth, as well as feeding difficulties and profound neurodevelopmental delay, muscle wasting, sensorineural deafness, optic atrophy, and progressive cardiomyopathy." | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005057497 | SCV005726191 | uncertain significance | not specified | 2024-11-19 | criteria provided, single submitter | clinical testing | Variant summary: OPA1 c.*4_*5+2delAAGT is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 2.7e-05 in 184752 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.*4_*5+2delAAGT in individuals affected with OPA1-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1184587). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Genomics England Pilot Project, |
RCV001542740 | SCV001760120 | likely pathogenic | Mitochondrial DNA depletion syndrome 14 (cardioencephalomyopathic type) | no assertion criteria provided | clinical testing |