rs5785040

Positions:

• chr10-54132840-TACACACAC-T
• chr10-54132840-TACACACAC-TAC
• chr10-54132840-TACACACAC-TACAC
• chr10-54132840-TACACACAC-TACACAC
• chr10-54132840-TACACACAC-TACACACACAC
• chr10-54132840-TACACACAC-TACACACACACAC
• chr10-54132840-TACACACAC-TACACACACACACAC
• chr10-54132840-TACACACAC-TACACACACACACACAC
• chr10-54132840-TACACACAC-TACACACACACACACACAC

Variant summary

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

The NM_033056.4(PCDH15):​c.1917+27_1917+34del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000601 in 1,496,272 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 0.0000066 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000059 (0 hom.)
• Consequence: PCDH15 NM_033056.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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	UniProt
PCDH15	NM_001384140.1	c.1917+27_1917+34del		intron_variant		ENST00000644397.2
PCDH15	NM_033056.4	c.1917+27_1917+34del		intron_variant		ENST00000320301.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000320301.11	c.1917+27_1917+34del		intron_variant		1	NM_033056.4
PCDH15	ENST00000644397.2	c.1917+27_1917+34del		intron_variant			NM_001384140.1

Frequencies

GnomAD3 genomes AF: 0.00000665 AC: 1 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: 0.00

Gnomad SAS AF: 0.000210

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000594 AC: 8 AN: 1345762 Hom.: 0 AF XY: 0.00000900 AC XY: 6 AN XY: 666798

Gnomad4 AFR exome AF: 0.0000327

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000291

Gnomad4 SAS exome AF: 0.0000643

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000179

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150510 Hom.: 0 Cov.: 0 AF XY: 0.0000136 AC XY: 1 AN XY: 73476

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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: rs5785040; hg19: chr10-55892600;