Variant: NM_016239.4(MYO15A):c.10045C>T (p.Gln3349Ter)

CA398643026

930033 (ClinVar)

Gene: MYO15A

Condition: nonsyndromic genetic deafness

Inheritance Mode: Autosomal recessive inheritance

UUID: 2747e39a-863a-4843-a4fd-29828d4c6759

HGVS expressions

NM_016239.4:c.10045C>T
NM_016239.4(MYO15A):c.10045C>T (p.Gln3349Ter)
NC_000017.11:g.18167686C>T
CM000679.2:g.18167686C>T
NC_000017.10:g.18071000C>T
CM000679.1:g.18071000C>T
NC_000017.9:g.18011725C>T
NG_011634.1:g.63981C>T
NG_011634.2:g.63981C>T
ENST00000642418.1:n.2309C>T
ENST00000643693.1:n.1847C>T
ENST00000644795.1:c.1837C>T
ENST00000646782.1:n.2779C>T
ENST00000647165.2:c.10045C>T
ENST00000651214.1:n.2476C>T
ENST00000205890.9:c.10045C>T
ENST00000418233.7:c.1837C>T
ENST00000433411.7:n.1495C>T
ENST00000445289.6:n.814C>T
ENST00000578575.1:n.447C>T
ENST00000579848.6:n.502+3848C>T
ENST00000615845.4:c.10045C>T
NM_016239.3:c.10045C>T

Pathogenic

• Met criteria codes: PM3_Supporting 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.10045C>T (p.Gln3349Ter) variant in the MYO15A gene is 0.002% (2/112392) 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). This variant has been detected in 1 patient with hearing loss in trans with a pathogenic variant (PM3_Supporting, Partners LMM internal data SCV001365783.1). The p.Gln3349Ter variant in MYO15A is predicted to cause a premature stop codon in biologically-relevant-exon 62/66 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 pathogenic for autosomal recessive hearing loss based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2_Supporting, PM3_Supporting, PVS1.

Met criteria codes

• PM3_Supporting: Found in one LMM patient compound heterozygous with Pathogenic variant (ClinVar ID: 930034), phase unconfirmed (0.5 PM3 points).
• PM2_Supporting: Present 0.002% (2/112392) European non-Finnish alleles in gnomAD v2.1.1, which meets the threshold to apply PM2_P (<0.007%)
• PVS1: Early termination codon in exon 62/66, NMD predicted, biologically relevant transcript.

Approved on: 2021-09-28

Published on: 2022-05-13