10-55154762-T-C

Position:

• chr10-55154762-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+11814A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 152,184 control chromosomes in the GnomAD database, including 67,663 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 0.94 (67663 hom., cov: 32)
• Consequence: PCDH15 NM_001354404.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.792

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001354404.2	c.-80+11814A>G		intron_variant			NP_001341333.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000458638.1	c.-80+11814A>G		intron_variant		5		ENSP00000394465
PCDH15	ENST00000613346.4	c.-80+11814A>G		intron_variant		4		ENSP00000481211

Frequencies

GnomAD3 genomes AF: 0.941 AC: 143132 AN: 152066 Hom.: 67639 Cov.: 32

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.995

Gnomad FIN AF: 0.990

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.975

Gnomad OTH AF: 0.951

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

GnomAD4 genome AF: 0.941 AC: 143206 AN: 152184 Hom.: 67663 Cov.: 32 AF XY: 0.943 AC XY: 70166 AN XY: 74392

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.966

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.995

Gnomad4 FIN AF: 0.990

Gnomad4 NFE AF: 0.975

Gnomad4 OTH AF: 0.951

Alfa AF: 0.973 Hom.: 117968

Bravo AF: 0.935

Asia WGS AF: 0.987 AC: 3427 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.7
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2799578; hg19: chr10-56914522;