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NM_206933.4(USH2A):c.13396C>T (p.Pro4466Ser) AND Usher syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 22, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001004775.4

Allele description [Variation Report for NM_206933.4(USH2A):c.13396C>T (p.Pro4466Ser)]

NM_206933.4(USH2A):c.13396C>T (p.Pro4466Ser)

Gene:
USH2A:usherin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q41
Genomic location:
Preferred name:
NM_206933.4(USH2A):c.13396C>T (p.Pro4466Ser)
Other names:
NM_206933.4(USH2A):c.13396C>T
HGVS:
  • NC_000001.11:g.215674515G>A
  • NG_009497.2:g.753934C>T
  • NM_206933.4:c.13396C>TMANE SELECT
  • NP_996816.3:p.Pro4466Ser
  • NC_000001.10:g.215847857G>A
  • NG_009497.1:g.753882C>T
  • NM_206933.2(USH2A):c.13396C>T
  • NM_206933.2:c.13396C>T
  • NM_206933.3:c.13396C>T
  • c.13396C>T
Protein change:
P4466S
Links:
dbSNP: rs138398671
NCBI 1000 Genomes Browser:
rs138398671
Molecular consequence:
  • NM_206933.4:c.13396C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Usher syndrome
Synonyms:
Usher Syndromes; Usher's syndrome
Identifiers:
MONDO: MONDO:0019501; MeSH: D052245; MedGen: C0271097; Orphanet: 886; OMIM: PS276900

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001164257ClinGen Hearing Loss Variant Curation Expert Panel
reviewed by expert panel

(Clingen Hl Acmg Specifications Cdh23 Coch Gjb2 Kcnq4 Myo6 Myo7a Slc26a4 Tecta Ush2a V2)		Uncertain significance
(Nov 22, 2022) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Hearing Loss Variant Curation Expert Panel, SCV001164257.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The variant NM_206933.4:c.13396C>T in USH2A is a missense variant predicted to cause substitution of proline by serine at amino acid 4466 (p.Pro4466Ser). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00044 (57/128120 alleles) in the European (non-Finnish) population, which does not meet either PM2_supporting nor BS1 criteria. The REVEL computational prediction analysis tool produced a score of 0.049, which is below the threshold necessary to apply BP4. This variant has been reported in two probands, one with retinitis pigmentosa, however the second variant was not specified and no PM3 points were awarded and the other homozygous with inherited retinal disease (PM3_Supporting; PMID 28041643, 32581362). In summary, the variant meets criteria to be classified as uncertain significance for AR Usher syndrome. ACMG/AMP criteria met, as specified by the ClinGen Hearing Loss VCEP: BP4, PM3_Supporting (ClinGen Hearing Loss VCEP specifications version 2; 11/22/2022)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024