rs10509024

chr10-55138066-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354404.2(PCDH15):c.-80+28510A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 152,206 control chromosomes in the GnomAD database, including 533 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.076 (533 hom., cov: 32)
• Consequence: PCDH15 NM_001354404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

Genes affected

PCDH15 (HGNC:14674): (protocadherin related 15) This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001354404.2	c.-80+28510A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000458638.1	c.-80+28510A>G		intron_variant		5
PCDH15	ENST00000613346.4	c.-80+28510A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11471 AN: 152086 Hom.: 525 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0461

Gnomad ASJ AF: 0.0799

Gnomad EAS AF: 0.0229

Gnomad SAS AF: 0.0377

Gnomad FIN AF: 0.0712

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0540

Gnomad OTH AF: 0.0746

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0755 AC: 11499 AN: 152206 Hom.: 533 Cov.: 32 AF XY: 0.0736 AC XY: 5476 AN XY: 74408

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0459

Gnomad4 ASJ AF: 0.0799

Gnomad4 EAS AF: 0.0228

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.0712

Gnomad4 NFE AF: 0.0540

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0591 Hom.: 203

Bravo AF: 0.0767

Asia WGS AF: 0.0420 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10509024; hg19: chr10-56897826;