10-54132840-TACACACAC-TACAC

Position:

• chr10-54132840-TACACACAC-TACAC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001384140.1(PCDH15):​c.1917+31_1917+34delGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000154 in 1,494,862 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: PCDH15 NM_001384140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.801

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_033056.4	c.1917+31_1917+34delGTGT		intron_variant		ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.1917+31_1917+34delGTGT		intron_variant		ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11	c.1917+31_1917+34delGTGT		intron_variant		1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.1917+31_1917+34delGTGT		intron_variant			NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.0000266 AC: 4 AN: 150402 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000589

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000114 AC: 16 AN: 140090 Hom.: 0 AF XY: 0.000108 AC XY: 8 AN XY: 73980

Gnomad AFR exome AF: 0.000106

Gnomad AMR exome AF: 0.0000467

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000620

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000121

Gnomad OTH exome AF: 0.000264

GnomAD4 exome AF: 0.0000141 AC: 19 AN: 1344460 Hom.: 0 AF XY: 0.0000180 AC XY: 12 AN XY: 666132

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000542

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000233

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000413

Gnomad4 NFE exome AF: 0.00000485

Gnomad4 OTH exome AF: 0.0000358

GnomAD4 genome AF: 0.0000266 AC: 4 AN: 150402 Hom.: 0 Cov.: 0 AF XY: 0.0000273 AC XY: 2 AN XY: 73358

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000589

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs5785040; hg19: chr10-55892600;