Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV001089559 | SCV001244796 | likely pathogenic | Autosomal recessive nonsyndromic hearing loss 3 | 2017-11-24 | criteria provided, single submitter | clinical testing | A heterozygous canonical splice site variant, NM_016239.3(MYO15A):c.10491+2T>C, has been identified in intron 65 of 66 of the MYO15A gene. This nucleotide substitution is predicted to cause aberrant splicing of exon66 in the MYO15A gene and may result in a truncated protein; further testing via RNA studies is required to confirm if splicing is altered. The variant is absent in population databases (gnomAD, dbSNP, 1000G) and has not been previously reported in clinical cases. Additionally, a truncating variant downstream of c.10491+2 in MYO15A has been reported as pathogenic in a family with this condition (ClinVar). Based on the information available at the time of curation, this variant has been classified as LIKELY PATHOGENIC. The presence of these two variants suggestscompound heterozygous mode of inheritance which is consistent with autosomal recessive deafness.NB: This variant has been reclassified to likely pathogenic due to confirmed compound heterozygosity. |