chr10-54132840-T-TACACAC

Position:

• chr10-54132840-T-TACACAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001384140.1(PCDH15):​c.1917+29_1917+34dupGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,494,628 control chromosomes in the GnomAD database, including 361 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (60 hom., cov: 0)
  • Exomes 𝑓: 0.038 (301 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-TACACAC is Benign according to our data. Variant chr10-54132840-T-TACACAC is described in ClinVar as [Benign]. Clinvar id is 1294168.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0264 (3976/150496) while in subpopulation NFE AF= 0.0421 (2839/67496). AF 95% confidence interval is 0.0408. There are 60 homozygotes in gnomad4. There are 1902 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 60 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_033056.4	c.1917+29_1917+34dupGTGTGT		intron_variant		ENST00000320301.11	NP_149045.3
PCDH15	NM_001384140.1	c.1917+29_1917+34dupGTGTGT		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+29_1917+34dupGTGTGT		intron_variant		1	NM_033056.4	ENSP00000322604.6
PCDH15	ENST00000644397.2	c.1917+29_1917+34dupGTGTGT		intron_variant			NM_001384140.1	ENSP00000495195.1

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 3983 AN: 150388 Hom.: 63 Cov.: 0

Gnomad AFR AF: 0.00692

Gnomad AMI AF: 0.0133

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.00923

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.0259

Gnomad MID AF: 0.0449

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0237

GnomAD3 exomes AF: 0.0375 AC: 5249 AN: 140090 Hom.: 23 AF XY: 0.0390 AC XY: 2887 AN XY: 73980

Gnomad AFR exome AF: 0.00795

Gnomad AMR exome AF: 0.0183

Gnomad ASJ exome AF: 0.0515

Gnomad EAS exome AF: 0.0152

Gnomad SAS exome AF: 0.0296

Gnomad FIN exome AF: 0.0327

Gnomad NFE exome AF: 0.0547

Gnomad OTH exome AF: 0.0448

GnomAD4 exome AF: 0.0379 AC: 50944 AN: 1344132 Hom.: 301 Cov.: 31 AF XY: 0.0379 AC XY: 25219 AN XY: 665982

Gnomad4 AFR exome AF: 0.00647

Gnomad4 AMR exome AF: 0.0161

Gnomad4 ASJ exome AF: 0.0379

Gnomad4 EAS exome AF: 0.00947

Gnomad4 SAS exome AF: 0.0238

Gnomad4 FIN exome AF: 0.0283

Gnomad4 NFE exome AF: 0.0422

Gnomad4 OTH exome AF: 0.0353

GnomAD4 genome AF: 0.0264 AC: 3976 AN: 150496 Hom.: 60 Cov.: 0 AF XY: 0.0259 AC XY: 1902 AN XY: 73470

Gnomad4 AFR AF: 0.00690

Gnomad4 AMR AF: 0.0152

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.00925

Gnomad4 SAS AF: 0.0220

Gnomad4 FIN AF: 0.0259

Gnomad4 NFE AF: 0.0421

Gnomad4 OTH AF: 0.0235

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 06, 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;