VCV000045913.41 - ClinVar

NM_022124.6(CDH23):c.3293A>G (p.Asn1098Ser)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(9)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_022124.6(CDH23):c.3293A>G (p.Asn1098Ser)

Variation ID: 45913 Accession: VCV000045913.41

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q22.1 10: 71712737 (GRCh38) [ NCBI UCSC ] 10: 73472494 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 9, 2018	Oct 20, 2024	Jan 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001164375.3:c.*3199T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		3 prime UTR
NM_022124.6:c.3293A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_071407.4:p.Asn1098Ser	missense
NM_001168390.2:c.*3199T>C		3 prime UTR
NM_001171930.2:c.3293A>G	NP_001165401.1:p.Asn1098Ser	missense
NC_000010.11:g.71712737A>G
NC_000010.10:g.73472494A>G
NG_008835.1:g.320791A>G

... more HGVS ... less HGVS

Protein change

N1098S

Other names

Canonical SPDI

NC_000010.11:71712736:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00100 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.00094

1000 Genomes Project 0.00100

The Genome Aggregation Database (gnomAD), exomes 0.00227

Exome Aggregation Consortium (ExAC) 0.00242

The Genome Aggregation Database (gnomAD) 0.00258

Trans-Omics for Precision Medicine (TOPMed) 0.00276

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00318

Links

ClinGen: CA137364 dbSNP: rs41281310 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
C10orf105	-	-	-	GRCh38 GRCh37	-	517
CDH23		-	-	GRCh38 GRCh37	4713	5559

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (1)	criteria provided, single submitter	May 7, 2012	RCV000039146.18
not provided	Benign/Likely benign (5)	criteria provided, multiple submitters, no conflicts	Jan 31, 2024	RCV000755903.38
Retinitis pigmentosa-deafness syndrome	Benign (1)	criteria provided, single submitter	May 28, 2019	RCV000988380.9
Usher syndrome type 1	Likely benign (1)	no assertion criteria provided	Jun 4, 2020	RCV001272558.9
CDH23-related disorder	Likely benign (1)	no assertion criteria provided	Apr 21, 2022	RCV004534829.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (May 07, 2012)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000062830.5 First in ClinVar: May 03, 2013 Last updated: Apr 09, 2018	Comment: Asn1098Ser in Exon 28 of CDH23: This variant is not expected to have clinical si gnificance because it has been identified in 0.4% (24/6836) of … (more) Asn1098Ser in Exon 28 of CDH23: This variant is not expected to have clinical si gnificance because it has been identified in 0.4% (24/6836) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs41281310). (less) Number of individuals with the variant: 13
Benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Retinitis pigmentosa-deafness syndrome Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001138074.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (Apr 23, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000714478.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the … (more) In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21078986, 27068579, 21228398, 18429043, 30245029) (less)
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001120985.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Likely benign (Nov 22, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000883553.4 First in ClinVar: Feb 18, 2019 Last updated: Feb 20, 2024
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005228197.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Likely benign (Feb 01, 2023)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV002585222.15 First in ClinVar: Oct 22, 2022 Last updated: Oct 20, 2024	Comment: CDH23: BP4, BS2 Number of individuals with the variant: 2
Likely benign (Jun 04, 2020)	no assertion criteria provided Method: clinical testing	Usher syndrome type 1 Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001454650.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021
Likely benign (Apr 21, 2022)	no assertion criteria provided Method: clinical testing	CDH23-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004749006.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Comment:

Asn1098Ser in Exon 28 of CDH23: This variant is not expected to have clinical si gnificance because it has been identified in 0.4% (24/6836) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs41281310).

Comment:

In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21078986, 27068579, 21228398, 18429043, 30245029)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs41281310 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_022124.6(CDH23):c.3293A>G (p.Asn1098Ser)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs41281310 ...