NM_022124.6(CDH23):c.1152C>A (p.Ser384Arg) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Nov 17, 2023
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:: RCV003481472.3

Allele description [Variation Report for NM_022124.6(CDH23):c.1152C>A (p.Ser384Arg)]

NM_022124.6(CDH23):c.1152C>A (p.Ser384Arg)

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.1152C>A (p.Ser384Arg)

Other names:

p.Ser384Arg

HGVS:

NC_000010.11:g.71645842C>A
NG_008835.1:g.253896C>A
NM_001171930.2:c.1152C>A
NM_001171931.2:c.1152C>A
NM_022124.6:c.1152C>AMANE SELECT
NM_052836.4:c.1152C>A
NP_001165401.1:p.Ser384Arg
NP_001165402.1:p.Ser384Arg
NP_071407.4:p.Ser384Arg
NP_443068.1:p.Ser384Arg
NC_000010.10:g.73405599C>A
NM_022124.5:c.1152C>A

Protein change:

S384R

Molecular consequence:

NM_001171930.2:c.1152C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171931.2:c.1152C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022124.6:c.1152C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_052836.4:c.1152C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004225736	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 9, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 27460420, 28902392, 32279305, 34997822, 25741868
SCV004291811	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27460420, 32279305, 34997822, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004225736

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 9, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004291811

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 17, 2023)

germline

clinical testing

PubMed (4)
[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	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Expanding the clinical and molecular spectrum of PRMT7 mutations: 3 additional patients and review.

Agolini E, Dentici ML, Bellacchio E, Alesi V, Radio FC, Torella A, Musacchia F, Tartaglia M, Dallapiccola B, Nigro V, Digilio MC, Novelli A.

Clin Genet. 2018 Mar;93(3):675-681. doi: 10.1111/cge.13137. Epub 2018 Feb 5. Review.

PubMed [citation]

PMID:: 28902392

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

See all PubMed Citations (6)

Details of each submission

From Mayo Clinic Laboratories, Mayo Clinic, SCV004225736.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (5)

Description

PP1_strong, PM2, PM3

#	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		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004291811.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 384 of the CDH23 protein (p.Ser384Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with deafness and/or Usher Syndrome (PMID: 27460420, 32279305, 34997822). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2501245). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CDH23 protein function with a negative predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Sep 29, 2024

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