chr10-71509962-C-T

Position:

• chr10-71509962-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_022124.6(CDH23):​c.146-120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,131,096 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (23 hom.)
• Consequence: CDH23 NM_022124.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.452

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]

CDH23-AS1 (HGNC:31433): (CDH23 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-71509962-C-T is Benign according to our data. Variant chr10-71509962-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1203837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71509962-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1982/152256) while in subpopulation AFR AF= 0.041 (1704/41530). AF 95% confidence interval is 0.0394. There are 40 homozygotes in gnomad4. There are 995 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 40 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.146-120C>T		intron_variant		ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.146-120C>T		intron_variant		5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1973 AN: 152138 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00216 AC: 2119 AN: 978840 Hom.: 23 Cov.: 13 AF XY: 0.00197 AC XY: 985 AN XY: 500664

Gnomad4 AFR exome AF: 0.0380

Gnomad4 AMR exome AF: 0.00319

Gnomad4 ASJ exome AF: 0.0160

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000317

Gnomad4 FIN exome AF: 0.0000227

Gnomad4 NFE exome AF: 0.000669

Gnomad4 OTH exome AF: 0.00509

GnomAD4 genome AF: 0.0130 AC: 1982 AN: 152256 Hom.: 40 Cov.: 32 AF XY: 0.0134 AC XY: 995 AN XY: 74438

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.00712

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0157 Hom.: 3

Bravo AF: 0.0148

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs116150071; hg19: chr10-73269719;