Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_206933.4(USH2A):c.9921T>G (p.Cys3307Trp)

Curation Version - 1.2
Curation History
JSON LD for Version 1.2

CA16044155

226441 (ClinVar)

Gene: USH2A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: f41fc1cd-9f60-4c2d-ae7d-a2b577765994

Approved on: 2024-02-21

Published on: 2024-04-01

HGVS expressions

NM_206933.4:c.9921T>G

NM_206933.4(USH2A):c.9921T>G (p.Cys3307Trp)

NC_000001.11:g.215798944A>C

CM000663.2:g.215798944A>C

NC_000001.10:g.215972286A>C

CM000663.1:g.215972286A>C

NC_000001.9:g.214038909A>C

NG_009497.1:g.629453T>G

NG_009497.2:g.629505T>G

ENST00000307340.8:c.9921T>G

ENST00000674083.1:c.9921T>G

ENST00000307340.7:c.9921T>G

NM_206933.2:c.9921T>G

NM_206933.3:c.9921T>G

Uncertain Significance

PM2_Supporting PM3

Evidence Links 0

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Criteria Specification: ClinGen Hearing Loss Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDH23, COCH, GJB2, KCNQ4, MYO6, MYO7A, SLC26A4, TECTA and USH2A Version 2

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The variant NM_206933.4:c.9921T>G in USH2A is a missense variant predicted to cause substitution of cysteine by tryptophan at amino acid 3307 (p.Cys3307Trp). The variant is absent from gnomAD v2.1.1 (PM2_Supporting). The REVEL computational prediction analysis tool produced a score of 0.585, which meets no codes. The variant has been reported in three compound heterozygous probands, two who were diagnosed with retinitis pigmentosa, and all with a likely pathogenic/pathogenic second USH2A variant in phase unknown (PM3; PMIDs: 32531858, 34906470, 36819107). In summary, this variant meets the criteria to be classified as uncertain significance for AR Usher syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP: PM2_Supporting, PM3. (ClinGen Hearing Loss VCEP specifications version 2; 2/21/2024).

PM2_Supporting

Variant is absent from gnomAD

PM3

Three probands from three publications have been found with the variant of interest and a second likely pathogenic/pathogenic USH2A variant.

Curation History

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