Variant: NM_016239.4(MYO15A):c.996C>G (p.Tyr332Ter)

CA8422996

505185 (ClinVar)

Gene: MYO15A

Condition: nonsyndromic genetic deafness

Inheritance Mode: Autosomal recessive inheritance

UUID: 5d598ebb-7674-454d-891d-d9ddfdccee01

HGVS expressions

NM_016239.4:c.996C>G
NM_016239.4(MYO15A):c.996C>G (p.Tyr332Ter)
NC_000017.11:g.18119796C>G
CM000679.2:g.18119796C>G
NC_000017.10:g.18023110C>G
CM000679.1:g.18023110C>G
NC_000017.9:g.17963835C>G
NG_011634.1:g.16091C>G
NG_011634.2:g.16091C>G
ENST00000647165.2:c.996C>G
ENST00000205890.9:c.996C>G
ENST00000583079.1:n.629C>G
ENST00000615845.4:c.996C>G
NM_016239.3:c.996C>G

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

• Met criteria codes: PM2_Supporting PVS1

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Evidence submitted by expert panel

Hearing Loss VCEP

The allele frequency of the c.996C>G (p.Tyr332Ter) variant in the MYO15A gene is 0.003% (3/112818) of European non-Finnish alleles by gnomAD v2.1.1, which is a low enough frequency to apply PM2_Supporting based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2_Supporting). The p.Tyr332Ter variant in MYO15A is predicted to cause a premature stop codon in biologically-relevant-exon 2/66 that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism (PVS1). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive hearing loss based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2_Supporting, PVS1.

Met criteria codes

• PM2_Supporting: Present in 0.003% (3/112818) of European non-Finnish alleles in gnomAD v2.1.1, which meets the threshold to apply PM2_P (<0.007%).
• PVS1: Premature stop codon in exon 2/66, which is a clinically significant exon.

Approved on: 2021-09-28

Published on: 2022-05-13