10-71799095-A-G

Position:

• chr10-71799095-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022124.6(CDH23):​c.7055-16A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 1,600,438 control chromosomes in the GnomAD database, including 81,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9720 hom., cov: 32)
  • Exomes 𝑓: 0.31 (71983 hom.)
• Consequence: CDH23 NM_022124.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.18

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-71799095-A-G is Benign according to our data. Variant chr10-71799095-A-G is described in ClinVar as [Benign]. Clinvar id is 46025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71799095-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH23	NM_022124.6	c.7055-16A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000224721.12	NP_071407.4
CDH23	NM_001171933.1	c.335-16A>G		splice_polypyrimidine_tract_variant, intron_variant			NP_001165404.1
CDH23	NM_001171934.1	c.335-16A>G		splice_polypyrimidine_tract_variant, intron_variant			NP_001165405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721.12	c.7055-16A>G		splice_polypyrimidine_tract_variant, intron_variant		5	NM_022124.6	ENSP00000224721	P1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52480 AN: 151946 Hom.: 9700 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.321

GnomAD3 exomes AF: 0.341 AC: 83505 AN: 244856 Hom.: 15695 AF XY: 0.326 AC XY: 43319 AN XY: 132846

Gnomad AFR exome AF: 0.451

Gnomad AMR exome AF: 0.444

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.622

Gnomad SAS exome AF: 0.270

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.305 AC: 441809 AN: 1448374 Hom.: 71983 Cov.: 33 AF XY: 0.301 AC XY: 216473 AN XY: 718976

Gnomad4 AFR exome AF: 0.450

Gnomad4 AMR exome AF: 0.434

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.664

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.313

GnomAD4 genome AF: 0.345 AC: 52537 AN: 152064 Hom.: 9720 Cov.: 32 AF XY: 0.348 AC XY: 25861 AN XY: 74344

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.280

Gnomad4 FIN AF: 0.346

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.319

Alfa AF: 0.294 Hom.: 1262

Bravo AF: 0.358

Asia WGS AF: 0.412 AC: 1434 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 12, 2009	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 27, 2017	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 12;C1832845:Usher syndrome type 1D;C4539685:Pituitary adenoma 5, multiple types Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 21, 2022

- -

Usher syndrome type 1D Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Autosomal recessive nonsyndromic hearing loss 12 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.072
DANN	Benign	0.28

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: rs4747193; hg19: chr10-73558852;