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NM_022124.6(CDH23):c.3625A>G (p.Thr1209Ala) AND not specified

Germline classification:
Benign (5 submissions)
Last evaluated:
Dec 20, 2021
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000039159.23

Allele description [Variation Report for NM_022124.6(CDH23):c.3625A>G (p.Thr1209Ala)]

NM_022124.6(CDH23):c.3625A>G (p.Thr1209Ala)

Genes:
CDH23:cadherin related 23 [Gene - OMIM - HGNC]
C10orf105:chromosome 10 open reading frame 105 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q22.1
Genomic location:
Preferred name:
NM_022124.6(CDH23):c.3625A>G (p.Thr1209Ala)
HGVS:
  • NC_000010.11:g.71730514A>G
  • NG_008835.1:g.338568A>G
  • NM_001168390.2:c.-6+7214T>C
  • NM_001171930.2:c.3625A>G
  • NM_022124.6:c.3625A>GMANE SELECT
  • NP_001165401.1:p.Thr1209Ala
  • NP_071407.4:p.Thr1209Ala
  • NP_071407.4:p.Thr1209Ala
  • NC_000010.10:g.73490271A>G
  • NM_022124.4:c.3625A>G
  • NM_022124.5:c.3625A>G
  • c.3625A>G
Protein change:
T1209A; THR1209ALA
Links:
OMIM: 605516.0013; dbSNP: rs41281314
NCBI 1000 Genomes Browser:
rs41281314
Molecular consequence:
  • NM_001168390.2:c.-6+7214T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001171930.2:c.3625A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_022124.6:c.3625A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
63

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000062843Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)
Benign
(Sep 3, 2010)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV000332788Eurofins Ntd Llc (ga)
criteria provided, single submitter

(EGL Classification Definitions 2015)
Benign
(Jul 10, 2015)
germlineclinical testing

Citation Link,

SCV000730521GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))
Benign
(Nov 3, 2017)
germlineclinical testing

Citation Link,

SCV001954136Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Benigngermlineclinical testing

SCV002051293Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Benign
(Dec 20, 2021)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided6363not providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Citations

PubMed

CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.

Astuto LM, Bork JM, Weston MD, Askew JW, Fields RR, Orten DJ, Ohliger SJ, Riazuddin S, Morell RJ, Khan S, Riazuddin S, Kremer H, van Hauwe P, Moller CG, Cremers CW, Ayuso C, Heckenlively JR, Rohrschneider K, Spandau U, Greenberg J, Ramesar R, Reardon W, et al.

Am J Hum Genet. 2002 Aug;71(2):262-75. Epub 2002 Jun 19.

PubMed [citation]
PMID:
12075507
PMCID:
PMC379159

Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans.

Zheng QY, Yan D, Ouyang XM, Du LL, Yu H, Chang B, Johnson KR, Liu XZ.

Hum Mol Genet. 2005 Jan 1;14(1):103-11. Epub 2004 Nov 10.

PubMed [citation]
PMID:
15537665
PMCID:
PMC2858222
See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000062843.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided63not providednot providedclinical testing PubMed (4)

Description

Thr1209Ala in exon 31 of CDH23: This variant has been identified in over 20% of a Black population (dbSNP rs41281314) and is therefore classified as benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided63not provided63not provided

From Eurofins Ntd Llc (ga), SCV000332788.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV000730521.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001954136.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002051293.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: CDH23 c.3625A>G (p.Thr1209Ala) results in a non-conservative amino acid change in the encoded protein sequence. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.011 in 249000 control chromosomes, predominantly at a frequency of 0.14 within the African or African-American subpopulation in the gnomAD database, including 170 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 43.38 fold of the estimated maximal expected allele frequency for a pathogenic variant in CDH23 causing Usher Syndrome phenotype (0.0032), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as benign.

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

Last Updated: May 19, 2024