chr10-71397124-TGCGAGCGGCGAGCG-T

Variant names:

• chr10-71397124-TGCGAGCGGCGAGCG-T
• rs527578984
• NM_022124.6:c.-183_-170delGAGCGGCGAGCGGC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_022124.6(CDH23):​c.-183_-170delGAGCGGCGAGCGGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 175,596 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00094 (1 hom.)
• Consequence: CDH23 NM_022124.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00126 (187/147854) while in subpopulation AFR AF= 0.00376 (151/40138). AF 95% confidence interval is 0.00327. There are 0 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH23	NM_022124.6	c.-183_-170delGAGCGGCGAGCGGC		5_prime_UTR_variant	Exon 1 of 70	ENST00000224721.12	NP_071407.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH23	ENST00000224721	c.-183_-170delGAGCGGCGAGCGGC		5_prime_UTR_variant	Exon 1 of 70	5	NM_022124.6	ENSP00000224721.9

Frequencies

GnomAD3 genomes AF: 0.00123 AC: 182 AN: 147726 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00365

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000802

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000442

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00725

Gnomad NFE AF: 0.000270

Gnomad OTH AF: 0.000975

GnomAD4 exome AF: 0.000937 AC: 26 AN: 27742 Hom.: 1 AF XY: 0.00110 AC XY: 20 AN XY: 18174

Gnomad4 AFR exome AF: 0.0119

Gnomad4 AMR exome AF: 0.00758

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00245

Gnomad4 FIN exome AF: 0.00151

Gnomad4 NFE exome AF: 0.000220

Gnomad4 OTH exome AF: 0.00196

GnomAD4 genome AF: 0.00126 AC: 187 AN: 147854 Hom.: 0 Cov.: 30 AF XY: 0.00141 AC XY: 102 AN XY: 72206

Gnomad4 AFR AF: 0.00376

Gnomad4 AMR AF: 0.000801

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000442

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000270

Gnomad4 OTH AF: 0.000964

ClinVar

Not reported in ClinVar

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: rs527578984; hg19: chr10-73156881;