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_022124.6(CDH23):c.2263C>T (p.His755Tyr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA137317

45891 (ClinVar)

Gene: CDH23

Condition: nonsyndromic genetic deafness

Link to MONDO

UUID: a25d23c2-e310-44b9-9600-d360176100dd

Approved on: 2020-01-15

Published on: 2020-01-15

HGVS expressions

NM_022124.6:c.2263C>T

NM_022124.6(CDH23):c.2263C>T (p.His755Tyr)

NC_000010.11:g.71694233C>T

CM000672.2:g.71694233C>T

NC_000010.10:g.73453990C>T

CM000672.1:g.73453990C>T

NC_000010.9:g.73123996C>T

NG_008835.1:g.302287C>T

NM_001171930.1:c.2263C>T

NM_001171931.1:c.2263C>T

NM_022124.5:c.2263C>T

NM_001171930.2:c.2263C>T

NM_001171931.2:c.2263C>T

ENST00000224721.10:c.2278C>T

ENST00000299366.11:c.2263C>T

ENST00000398809.8:c.2263C>T

ENST00000442677.3:n.1038C>T

ENST00000466757.7:n.1694C>T

ENST00000616684.4:c.2263C>T

ENST00000622827.4:c.2263C>T

Benign

BA1

BP4

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 of the c.2263C>T (p.His755Tyr) variant in CDH23 is 0.73% (248/30558) 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). Of note, this variant was reported in 2 individuals with Usher syndrome, though without any evidence of pathogenicity (PM3 not met; PMID: 18429043, 21569298). In summary, this variant meets criteria to be classified as benign based on the ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel (BA1).

BA1

This variant is present in 0.73% (filtering AF 95%) of South Asian chromosomes in gnomAD v2.1.1.

BP4

The residue is not highly conserved (several vertebrates have Proline at this position) and the REVEL score is 0.211.

Curation History

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