10-53808767-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001142769.3(PCDH15):c.5298G>A(p.Ala1766Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00787 in 1,612,442 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0080 ( 52 hom. )

Consequence

PCDH15
NM_001142769.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.507

Variant links:

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]

PCDH15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 10-53808767-C-T is Benign according to our data. Variant chr10-53808767-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 44037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53808767-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.507 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00702 (1068/152200) while in subpopulation NFE AF= 0.00824 (560/68000). AF 95% confidence interval is 0.00767. There are 6 homozygotes in gnomad4. There are 568 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH15	NM_001384140.1 link	c.4672-1637G>A		intron_variant	Intron 37 of 37	ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000644397.2 link	c.4672-1637G>A		intron_variant	Intron 37 of 37		NM_001384140.1	ENSP00000495195.1		A0A2R8Y6C0

Frequencies

GnomAD3 genomes

AF:

0.00702

AC:

1067

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00662

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0182

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00823

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00699

AC:

1718

AN:

245870

Hom.:

AF XY:

0.00693

AC XY:

926

AN XY:

133562

show subpopulations

Gnomad AFR exome

AF:

0.00741

Gnomad AMR exome

AF:

0.000704

Gnomad ASJ exome

AF:

0.00222

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000666

Gnomad FIN exome

AF:

0.0190

Gnomad NFE exome

AF:

0.0100

Gnomad OTH exome

AF:

0.00567

GnomAD4 exome

AF:

0.00796

AC:

11629

AN:

1460242

Hom.:

Cov.:

AF XY:

0.00776

AC XY:

5636

AN XY:

726220

show subpopulations

Gnomad4 AFR exome

AF:

0.00816

Gnomad4 AMR exome

AF:

0.000742

Gnomad4 ASJ exome

AF:

0.00226

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0195

Gnomad4 NFE exome

AF:

0.00884

Gnomad4 OTH exome

AF:

0.00638

GnomAD4 genome

AF:

0.00702

AC:

1068

AN:

152200

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

568

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00662

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0182

Gnomad4 NFE

AF:

0.00824

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00705

Hom.:

Bravo

AF:

0.00566

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Feb 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PCDH15: BP4, BP7, BS2 -

Jul 02, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 18, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:2

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ala1766Ala in Exon 37A of PCDH15: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 0.7% (40/5446) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs139441645). -

Feb 11, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.9

DANN

Benign

0.78

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over