10-71724016-G-A

Variant names:

• chr10-71724016-G-A
• rs72817951
• NM_022124.6:c.3370-29G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022124.6(CDH23):​c.3370-29G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 1,552,824 control chromosomes in the GnomAD database, including 3,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (232 hom., cov: 33)
  • Exomes 𝑓: 0.066 (3453 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.37
• Publications: 4 publications found

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]

C10orf105 (HGNC:20304): (chromosome 10 open reading frame 105) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-71724016-G-A is Benign according to our data. Variant chr10-71724016-G-A is described in ClinVar as [Benign]. Clinvar id is 261547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.3370-29G>A		intron_variant	Intron 28 of 69	ENST00000224721.12	NP_071407.4
CDH23	NM_001171930.2	c.3370-29G>A		intron_variant	Intron 28 of 31		NP_001165401.1
C10orf105	NM_001168390.2	c.-5-7674C>T		intron_variant	Intron 1 of 1		NP_001161862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.3370-29G>A		intron_variant	Intron 28 of 69	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7171 AN: 152200 Hom.: 232 Cov.: 33

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0742

Gnomad OTH AF: 0.0521

GnomAD2 exomes AF: 0.0441 AC: 6924 AN: 156900 AF XY: 0.0429

Gnomad AFR exome AF: 0.0136

Gnomad AMR exome AF: 0.0312

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0656

Gnomad NFE exome AF: 0.0713

Gnomad OTH exome AF: 0.0512

GnomAD4 exome AF: 0.0658 AC: 92142 AN: 1400506 Hom.: 3453 Cov.: 31 AF XY: 0.0639 AC XY: 44177 AN XY: 690910

African (AFR) AF: 0.0106 AC: 335 AN: 31692

American (AMR) AF: 0.0337 AC: 1207 AN: 35842

Ashkenazi Jewish (ASJ) AF: 0.0255 AC: 642 AN: 25192

East Asian (EAS) AF: 0.0000557 AC: 2 AN: 35898

South Asian (SAS) AF: 0.00782 AC: 620 AN: 79282

European-Finnish (FIN) AF: 0.0638 AC: 3150 AN: 49350

Middle Eastern (MID) AF: 0.00860 AC: 49 AN: 5698

European-Non Finnish (NFE) AF: 0.0766 AC: 82733 AN: 1079468

Other (OTH) AF: 0.0586 AC: 3404 AN: 58084

GnomAD4 genome AF: 0.0471 AC: 7169 AN: 152318 Hom.: 232 Cov.: 33 AF XY: 0.0451 AC XY: 3358 AN XY: 74476

African (AFR) AF: 0.0118 AC: 491 AN: 41558

American (AMR) AF: 0.0441 AC: 675 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4832

European-Finnish (FIN) AF: 0.0681 AC: 723 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0742 AC: 5050 AN: 68016

Other (OTH) AF: 0.0510 AC: 108 AN: 2116

Alfa AF: 0.0447 Hom.: 81

Bravo AF: 0.0438

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.1
DANN	Benign	0.84
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs72817951; hg19: chr10-73483773;