ClinVar Miner

Submissions for variant NM_016239.4(MYO15A):c.10247CCT[1] (p.Ser3417del)

dbSNP: rs760069953
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV001089558 SCV001244795 likely pathogenic Autosomal recessive nonsyndromic hearing loss 3 2017-08-22 criteria provided, single submitter clinical testing A heterozygous in-frame deletion variant was identified in exon 64 of MYO15A, NM_016239.3(MYO15A):c.10250_10252delCCT.This deletionresults in the lossof a serineat codon position 3417, NP_057323.3(MYO15A):p.(Ser3417del). The serine at this position has very high conservation (100 vertebrates, UCSC). It is situated in the FERM domain. This variant is present in the gnomAD population database at a frequency of 0.002%. It has not been previously observed in other clinical cases. Based on current information and in association with the NM_016239.3(MYO15A):c.9371dupA deletion variant, this variant has been classified as LIKELY PATHOGENIC.Parental testingindicates the variants are in trans. The presence of these two variants suggests a possible compound heterozygous mode of inheritance which is consistent with autosomal recessive deafness 3.NB: This variant has been reclassified from Class 3A (VUS with high clinical significance)to Class 4 (likely pathogenic).
Molecular Diagnosis Center for Deafness RCV001089558 SCV001984912 pathogenic Autosomal recessive nonsyndromic hearing loss 3 criteria provided, single submitter clinical testing
GeneDx RCV001759858 SCV001986243 uncertain significance not provided 2020-09-23 criteria provided, single submitter clinical testing In-frame deletion of 1 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25792667, 29482514, 31581539, 31827275, 30896630)
3billion RCV001089558 SCV002572658 likely pathogenic Autosomal recessive nonsyndromic hearing loss 3 2022-09-01 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). This variant leads to inframe deletion located in a nonrepeat region that it is predicted to change the length of the protein and disrupt normal protein function. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000869466 / PMID: 25792667). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Invitae RCV001759858 SCV004298179 pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This variant, c.10250_10252del, results in the deletion of 1 amino acid(s) of the MYO15A protein (p.Ser3417del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs760069953, gnomAD 0.04%). This variant has been observed in individual(s) with deafness (PMID: 25792667, 29482514, 30896630, 34265623, 35346193). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as c.10249_10251delTCC (p.F3417del) or c.10245_10247delCTC. ClinVar contains an entry for this variant (Variation ID: 869466). For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.