10-54188194-T-G

Position:

• chr10-54188194-T-G

Variant summary

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

The NM_033056.4(PCDH15):​c.1306-2926A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,796 control chromosomes in the GnomAD database, including 4,765 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 0.21 (4765 hom., cov: 33)
• Consequence: PCDH15 NM_033056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.63

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001384140.1	c.1306-2926A>C		intron_variant		ENST00000644397.2	NP_001371069.1
PCDH15	NM_033056.4	c.1306-2926A>C		intron_variant		ENST00000320301.11	NP_149045.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.1306-2926A>C		intron_variant		1	NM_033056.4	ENSP00000322604
PCDH15	ENST00000644397.2	c.1306-2926A>C		intron_variant			NM_001384140.1	ENSP00000495195

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32117 AN: 151676 Hom.: 4764 Cov.: 33

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.212 AC: 32140 AN: 151796 Hom.: 4765 Cov.: 33 AF XY: 0.222 AC XY: 16494 AN XY: 74168

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.220

Alfa AF: 0.0860 Hom.: 104

Bravo AF: 0.219

Asia WGS AF: 0.596 AC: 2064 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.5
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: rs10825264; hg19: chr10-55947954;