Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: CDH23 vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

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

CA137317

45891 (ClinVar)

Gene: CDH23
Condition: nonsyndromic genetic deafness
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: a25d23c2-e310-44b9-9600-d360176100dd
Approved on: 2024-12-18
Published on: 2025-03-28

HGVS expressions

NM_022124.6:c.2263C>T
NM_022124.6(CDH23):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
ENST00000224721.12:c.2263C>T
ENST00000398809.9:c.2263C>T
ENST00000442677.4:c.2263C>T
ENST00000466757.8:c.1694C>T
ENST00000224721.10:c.2278C>T
ENST00000299366.11:c.2263C>T
ENST00000398809.8:c.2263C>T
ENST00000442677.3:c.1038C>T
ENST00000466757.7:c.1694C>T
ENST00000616684.4:c.2263C>T
ENST00000622827.4:c.2263C>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
More

Benign

Met criteria codes 1
BA1
Not Met criteria codes 1
BP4

Evidence Links 0

Expert Panel

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_022124.6:c.2263C>T in CDH23 is a missense variant predicted to cause substitution of histidine by tyrosine at amino acid 755 (p.His755Tyr). The highest population minor allele frequency in gnomAD v4.1.0 is 0.008578 (781/91042 alleles, 11 homozygotes) for the South Asian population, which is higher than the ClinGen Hearing Loss CDH23 threshold (≥0.005) for BA1, and therefore meets this criterion (BA1). The REVEL computational prediction analysis tool produced a score of 0.211, which meets no codes. This variant was reported in 2 individuals with Usher syndrome and one with Retinitis Pigmentosa, though without any evidence of pathogenicity (PM3 not met; PMIDs: 18429043, 21569298, 30718709). 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. (ClinGen Hearing Loss VCEP specifications version 2; 12/18/2024).
Met criteria codes
BA1
The highest population minor allele frequency in gnomAD v4.1.0 is 0.008578 (781/91042 alleles, 11 homozygotes) for the South Asian population
Not Met criteria codes
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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