NM_022124.6(CDH23):c.871G>A (p.Gly291Arg) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Oct 26, 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:: RCV001376753.8

Allele description [Variation Report for NM_022124.6(CDH23):c.871G>A (p.Gly291Arg)]

NM_022124.6(CDH23):c.871G>A (p.Gly291Arg)

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.871G>A (p.Gly291Arg)

HGVS:

NC_000010.11:g.71615542G>A
NG_008835.1:g.223596G>A
NM_001171930.2:c.871G>A
NM_001171931.2:c.871G>A
NM_001171932.2:c.871G>A
NM_022124.6:c.871G>AMANE SELECT
NM_052836.4:c.871G>A
NP_001165401.1:p.Gly291Arg
NP_001165402.1:p.Gly291Arg
NP_001165403.1:p.Gly291Arg
NP_071407.4:p.Gly291Arg
NP_443068.1:p.Gly291Arg
NC_000010.10:g.73375299G>A
NM_022124.5:c.871G>A

Protein change:

G291R

Links:

dbSNP: rs767343063

NCBI 1000 Genomes Browser:

rs767343063

Molecular consequence:

NM_001171930.2:c.871G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171931.2:c.871G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171932.2:c.871G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022124.6:c.871G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_052836.4:c.871G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens isolate CHM13 chromosome 6, alternate assembly T2T-CHM13v2.0
Homo sapiens isolate CHM13 chromosome 6, alternate assembly T2T-CHM13v2.0
gi|2194974009|gnl|ASM:GCF_009914825 f|NC_060930.1||gpp|GPC_000012745.1||gnl|NCBI_GENOMES|119566

Nucleotide
PREDICTED: Homo sapiens BEN domain containing 7 (BEND7), transcript variant X23,...
PREDICTED: Homo sapiens BEN domain containing 7 (BEND7), transcript variant X23, mRNA
gi|2217276074|ref|XM_047424796.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001573914	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 17, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25404053, 27583663, 32860223, 28492532
SCV001813708	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Oct 26, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001573914

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 17, 2023)

germline

clinical testing

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

SCV001813708

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Oct 26, 2023)

germline

clinical testing

Citation Link

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	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Targeted next generation sequencing for molecular diagnosis of Usher syndrome.

Aparisi MJ, Aller E, Fuster-García C, García-García G, Rodrigo R, Vázquez-Manrique RP, Blanco-Kelly F, Ayuso C, Roux AF, Jaijo T, Millán JM.

Orphanet J Rare Dis. 2014 Nov 18;9:168. doi: 10.1186/s13023-014-0168-7.

PubMed [citation]

PMID:: 25404053
PMCID:: PMC4245769

Diversity of the Genes Implicated in Algerian Patients Affected by Usher Syndrome.

Abdi S, Bahloul A, Behlouli A, Hardelin JP, Makrelouf M, Boudjelida K, Louha M, Cheknene A, Belouni R, Rous Y, Merad Z, Selmane D, Hasbelaoui M, Bonnet C, Zenati A, Petit C.

PLoS One. 2016;11(9):e0161893. doi: 10.1371/journal.pone.0161893.

PubMed [citation]

PMID:: 27583663
PMCID:: PMC5008642

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001573914.4

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CDH23 protein function. ClinVar contains an entry for this variant (Variation ID: 1065907). This missense change has been observed in individuals with clinical features of Usher syndrome (PMID: 25404053, 27583663, 32860223; Invitae). This variant is present in population databases (rs767343063, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 291 of the CDH23 protein (p.Gly291Arg).

#	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 GeneDx, SCV001813708.2

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 36460718, 32860223, 27583663, 25404053)

#	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: Feb 14, 2024

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