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: USH2A 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_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: 2025-03-12
Published on: 2025-03-28

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
ENST00000307340.8:c.7334C>T
ENST00000674083.1:c.7334C>T
ENST00000307340.7:c.7334C>T
NM_206933.2:c.7334C>T
NM_206933.4:c.7334C>T
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Benign

Met criteria codes 1
BA1
Not Met criteria codes 3
BP4 PP3 PM3

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_206933.4:c.7334C>T in USH2A is a missense variant predicted to cause substitution of serine by phenylalanine at amino acid 2445 (p.Ser2445Phe). The highest population minor allele frequency in gnomAD v4.1.0 is 0.0054 (489/91072 alleles, 3 homozygotes) for the South Asian population, which is higher than the ClinGen Hearing Loss USH2A threshold (≥0.005) for BA1, and therefore meets this criterion (BA1). The REVEL computational prediction analysis tool produced a score of 0.358, which meets no codes. This variant was reported in one individual with Usher syndrome and one with Retinitis Pigmentosa, though without any evidence of pathogenicity (PM3 not met; PMIDs: 28041643, 33926394). 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; 3/12/2025).
Met criteria codes
BA1
The highest population minor allele frequency in gnomAD v4.1.0 is 0.0054 (489/91072 alleles, 3 homozygotes) for the South Asian population, which is higher than the ClinGen Hearing Loss USH2A threshold (≥0.005) for BA1
Not Met criteria codes
BP4
The REVEL computational prediction analysis tool produced a score of 0.358, which meets no codes
PP3
The REVEL computational prediction analysis tool produced a score of 0.358, which meets no codes
PM3
This variant was reported in one individual with Usher syndrome and one with Retinitis Pigmentosa, though without any evidence of pathogenicity.
Curation History
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