NM_022124.6(CDH23):c.2236G>A (p.Val746Ile) AND Usher syndrome type 1D

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 8, 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:: RCV001105265.5

Allele description [Variation Report for NM_022124.6(CDH23):c.2236G>A (p.Val746Ile)]

NM_022124.6(CDH23):c.2236G>A (p.Val746Ile)

Gene:

CDH23:cadherin related 23 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.1

Genomic location:

Preferred name:

NM_022124.6(CDH23):c.2236G>A (p.Val746Ile)

HGVS:

NC_000010.11:g.71694206G>A
NG_008835.1:g.302260G>A
NM_001171930.2:c.2236G>A
NM_001171931.2:c.2236G>A
NM_022124.6:c.2236G>AMANE SELECT
NP_001165401.1:p.Val746Ile
NP_001165402.1:p.Val746Ile
NP_071407.4:p.Val746Ile
NC_000010.10:g.73453963G>A
NM_022124.5:c.2236G>A

Protein change:

V746I

Links:

dbSNP: rs550384315

NCBI 1000 Genomes Browser:

rs550384315

Molecular consequence:

NM_001171930.2:c.2236G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171931.2:c.2236G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022124.6:c.2236G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Usher syndrome type 1D (USH1D)
Synonyms:: USHER SYNDROME, TYPE ID
Identifiers:: MONDO: MONDO:0010984; MedGen: C1832845; Orphanet: 231169; Orphanet: 886; OMIM: 601067

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001262205	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 28, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001572163	Ocular Genomics Institute, Massachusetts Eye and Ear	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 8, 2021)	germline	research	PubMed (2) [See all records that cite these PMIDs] 18429043, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001262205

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 28, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV001572163

Ocular Genomics Institute, Massachusetts Eye and Ear

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 8, 2021)

germline

research

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutation profile of the CDH23 gene in 56 probands with Usher syndrome type I.

Oshima A, Jaijo T, Aller E, Millan JM, Carney C, Usami S, Moller C, Kimberling WJ.

Hum Mutat. 2008 Jun;29(6):E37-46. doi: 10.1002/humu.20761.

PubMed [citation]

PMID:: 18429043
PMCID:: PMC2399895

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001262205.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ocular Genomics Institute, Massachusetts Eye and Ear, SCV001572163.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

Description

The CDH23 c.2236G>A variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2. Based on this evidence we have classified this variant as Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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