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]

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Variant: NM_206933.3(USH2A):c.7334C>T (p.Ser2445Phe)

CA143592

48581 (ClinVar)

Gene: USH2A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 56dae361-9fdd-4622-a232-aaf252443c65

Approved on: 2020-03-18

Published on: 2020-03-19

HGVS expressions

NM_206933.3:c.7334C>T

NM_206933.3(USH2A):c.7334C>T (p.Ser2445Phe)

NC_000001.11:g.215900872G>A

CM000663.2:g.215900872G>A

NC_000001.10:g.216074214G>A

CM000663.1:g.216074214G>A

NC_000001.9:g.214140837G>A

NG_009497.1:g.527525C>T

NG_009497.2:g.527577C>T

NM_206933.2:c.7334C>T

NM_206933.4:c.7334C>T

ENST00000307340.7:c.7334C>T

Benign

BA1

BP4 PM3

Evidence Links 0

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The filtering allele frequency (the lower threshold of the 95% CI of 197/30616) of the p.Ser2445Phe variant in the USH2A gene is 0.57% for South Asian chromosomes by gnomAD v2.1.1, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1).

BA1

The variant is present in 0.57% (197/30616) (95% CI) of South Asian chromosomes by gnomAD v2.1.1 and in 0.57% (25/3038) (95% CI) of South Asian chromosomes by gnomAD v3.

BP4

REVEL score is 0.358 and mouse, rat, and prairie vole have an Ala residue at this position.

PM3

This variant was found in an individual sequenced at LMM. The individual also was heterozygous for the c.8431C>A (p.Pro2811Thr) variant in USH2A, the c.7442C>G (p.Pro2481Arg) variant in CDH23, and the c.4471G>A (p.Val1491Met) variant in MYO7A. The p.Pro2811Thr variant has a very high MAF in gnomAD v2.1.1 suggesting this variant is also benign. For this reason, this case was not given PM3 points.

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