Variant: NM_206933.3(USH2A):c.2081G>A (p.Cys694Tyr)

CA1396311

418533 (ClinVar)

Gene: USH2A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

UUID: 25255e2d-61ae-4965-aa8b-19b4610689ce

Approved on: 2020-01-21

Published on: 2020-01-21

HGVS expressions

NM_206933.3:c.2081G>A
NM_206933.3(USH2A):c.2081G>A (p.Cys694Tyr)
NC_000001.11:g.216250989C>T
CM000663.2:g.216250989C>T
NC_000001.10:g.216424331C>T
CM000663.1:g.216424331C>T
NC_000001.9:g.214490954C>T
NG_009497.1:g.177408G>A
NG_009497.2:g.177460G>A
ENST00000307340.8:c.2081G>A
ENST00000674083.1:c.2081G>A
ENST00000307340.7:c.2081G>A
ENST00000366942.3:c.2081G>A
NM_007123.5:c.2081G>A
NM_206933.2:c.2081G>A
NM_007123.6:c.2081G>A
NM_206933.4:c.2081G>A

Likely Pathogenic

• Met criteria codes: PP3 PP4 PM2 PM3

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Evidence submitted by expert panel

Hearing Loss VCEP

The c.2081G>A (p.Cys694Tyr) variant in USH2A is present in 0.0003% (the lower threshold of the 95% CI of 2/113290) European alleles (gnomAD v2.1.1), which is low enough frequency to apply PM2 based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive Usher syndrome (PM2). This variant has been detected in at least 1 patient with Usher syndrome in whom a pathogenic or suspected-pathogenic variant was observed in trans (PM3; VCV000002351.6; PMID: 28041643). The patient displayed features of hearing loss and retinitis pigmentosa, which is highly specific for USH2A (PP4; PMID: 28041643). The REVEL computational prediction analysis tool produced a score of 0.92 (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive & Usher syndrome based on the ACMG/AMP criteria applied as specified by the Hearing Loss Expert Panel (PM2, PM3, PP4, PP3).

Met criteria codes

• PP3: REVEL .92 No predicted splicing impact Evolutionarily conserved
• PM2: 0.0017% (2/113290) European alleles in gnomAD v2.1.1 0.0023% (1/42036) African and (1/64576) European alleles in gnomAD v3