chr10-54132840-T-TACACACAC

Position:

• chr10-54132840-T-TACACACAC

Variant summary

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

The NM_001384140.1(PCDH15):​c.1917+27_1917+34dupGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,496,160 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00020 (1 hom.)
• Consequence: PCDH15 NM_001384140.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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+27_1917+34dupGTGTGTGT		intron_variant		ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.1917+27_1917+34dupGTGTGTGT		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+27_1917+34dupGTGTGTGT		intron_variant		1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.1917+27_1917+34dupGTGTGTGT		intron_variant			NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.000206 AC: 31 AN: 150400 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000968

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000271 AC: 38 AN: 140090 Hom.: 0 AF XY: 0.000243 AC XY: 18 AN XY: 73980

Gnomad AFR exome AF: 0.000530

Gnomad AMR exome AF: 0.000187

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000723

Gnomad SAS exome AF: 0.000590

Gnomad FIN exome AF: 0.0000764

Gnomad NFE exome AF: 0.000173

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000202 AC: 272 AN: 1345652 Hom.: 1 Cov.: 31 AF XY: 0.000207 AC XY: 138 AN XY: 666748

Gnomad4 AFR exome AF: 0.000392

Gnomad4 AMR exome AF: 0.000217

Gnomad4 ASJ exome AF: 0.0000837

Gnomad4 EAS exome AF: 0.000989

Gnomad4 SAS exome AF: 0.000515

Gnomad4 FIN exome AF: 0.000165

Gnomad4 NFE exome AF: 0.000159

Gnomad4 OTH exome AF: 0.0000716

GnomAD4 genome AF: 0.000206 AC: 31 AN: 150508 Hom.: 0 Cov.: 0 AF XY: 0.000177 AC XY: 13 AN XY: 73474

Gnomad4 AFR AF: 0.000293

Gnomad4 AMR AF: 0.000132

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00138

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000968

Gnomad4 NFE AF: 0.000133

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;