10-54132840-T-TACAC

Position:

• chr10-54132840-T-TACAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001384140.1(PCDH15):​c.1917+31_1917+34dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,493,460 control chromosomes in the GnomAD database, including 6,173 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1496 hom., cov: 0)
  • Exomes 𝑓: 0.11 (4677 hom.)
• Consequence: PCDH15 NM_001384140.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 Benign. Variant got -10 ACMG points.

• BP6: Variant 10-54132840-T-TACAC is Benign according to our data. Variant chr10-54132840-T-TACAC is described in ClinVar as [Benign]. Clinvar id is 1294167.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_033056.4	c.1917+31_1917+34dupGTGT		intron_variant		ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.1917+31_1917+34dupGTGT		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+34dupGTGT		intron_variant		1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.1917+31_1917+34dupGTGT		intron_variant			NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15431 AN: 150344 Hom.: 1502 Cov.: 0

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.0266

Gnomad AMR AF: 0.0658

Gnomad ASJ AF: 0.0682

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.0861

Gnomad OTH AF: 0.0887

GnomAD3 exomes AF: 0.148 AC: 20784 AN: 140090 Hom.: 790 AF XY: 0.156 AC XY: 11530 AN XY: 73980

Gnomad AFR exome AF: 0.0655

Gnomad AMR exome AF: 0.0792

Gnomad ASJ exome AF: 0.0962

Gnomad EAS exome AF: 0.439

Gnomad SAS exome AF: 0.235

Gnomad FIN exome AF: 0.195

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.109 AC: 146512 AN: 1343008 Hom.: 4677 Cov.: 31 AF XY: 0.111 AC XY: 74098 AN XY: 665366

Gnomad4 AFR exome AF: 0.0572

Gnomad4 AMR exome AF: 0.0656

Gnomad4 ASJ exome AF: 0.0722

Gnomad4 EAS exome AF: 0.479

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.152

Gnomad4 NFE exome AF: 0.0919

Gnomad4 OTH exome AF: 0.116

GnomAD4 genome AF: 0.102 AC: 15415 AN: 150452 Hom.: 1496 Cov.: 0 AF XY: 0.111 AC XY: 8124 AN XY: 73448

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.0656

Gnomad4 ASJ AF: 0.0682

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.0861

Gnomad4 OTH AF: 0.0887

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 18, 2019

- -

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;