rs149704197

Positions:

• chr10-71812624-GTCAGGCA-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_022124.6(CDH23):​c.9510+19_9510+25del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,613,816 control chromosomes in the GnomAD database, including 178 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.020 (93 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (85 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:7
• Conservation: PhyloP100: -0.0120

Genes affected

CDH23 (HGNC:13733): (cadherin related 23) This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described. [provided by RefSeq, May 2013]

LOC124902446 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 10-71812624-GTCAGGCA-G is Benign according to our data. Variant chr10-71812624-GTCAGGCA-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 133306.We mark this variant Likely_benign, oryginal submissions are: {Benign=6, Uncertain_significance=1}. Variant chr10-71812624-GTCAGGCA-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH23	NM_022124.6	c.9510+19_9510+25del		intron_variant		ENST00000224721.12
LOC124902446	XR_007062185.1	n.128_134del		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH23	ENST00000224721.12	c.9510+19_9510+25del		intron_variant		5	NM_022124.6	P1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2994 AN: 152242 Hom.: 93 Cov.: 33

Gnomad AFR AF: 0.0676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00889

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0143

GnomAD3 exomes AF: 0.00507 AC: 1261 AN: 248640 Hom.: 30 AF XY: 0.00403 AC XY: 544 AN XY: 135022

Gnomad AFR exome AF: 0.0683

Gnomad AMR exome AF: 0.00403

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000444

Gnomad OTH exome AF: 0.00265

GnomAD4 exome AF: 0.00206 AC: 3014 AN: 1461456 Hom.: 85 AF XY: 0.00183 AC XY: 1327 AN XY: 727036

Gnomad4 AFR exome AF: 0.0684

Gnomad4 AMR exome AF: 0.00411

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000225

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.0197 AC: 2995 AN: 152360 Hom.: 93 Cov.: 33 AF XY: 0.0193 AC XY: 1440 AN XY: 74514

Gnomad4 AFR AF: 0.0675

Gnomad4 AMR AF: 0.00888

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00995 Hom.: 9

Bravo AF: 0.0222

Asia WGS AF: 0.00404 AC: 15 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:7

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Usher syndrome type 1D Uncertain:1

Uncertain significance, criteria provided, single submitter

literature only

Molecular Genetics Laboratory; Baylor College of Medicine

-

- -

Atypical Gaucher Disease Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 16, 2017

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. -

Combined PSAP deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Usher syndrome type 1 Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Galactosylceramide beta-galactosidase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Metachromatic leukodystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149704197; hg19: chr10-73572381;