Variant 10-54132840-TACACACAC-TACACAC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001384140.1(PCDH15):c.1917+33_1917+34delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 1,371,676 control chromosomes in the GnomAD database, including 795 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 233 hom., cov: 0)

Exomes 𝑓: 0.035 ( 562 hom. )

Consequence

PCDH15
NM_001384140.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0900

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 10-54132840-TAC-T is Benign according to our data. Variant chr10-54132840-TAC-T is described in ClinVar as [Benign]. Clinvar id is 227006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-54132840-TAC-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_033056.4 linkuse as main transcript	c.1917+33_1917+34delGT		intron_variant		ENST00000320301.11	NP_149045.3	Q96QU1-1
PCDH15	NM_001384140.1 linkuse as main transcript	c.1917+33_1917+34delGT		intron_variant		ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11 linkuse as main transcript	c.1917+33_1917+34delGT		intron_variant		1	NM_033056.4	ENSP00000322604.6		Q96QU1-1
PCDH15	ENST00000644397.2 linkuse as main transcript	c.1917+33_1917+34delGT		intron_variant			NM_001384140.1	ENSP00000495195.1		A0A2R8Y6C0

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6758

AN:

150298

Hom.:

233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0896

Gnomad AMI

AF:

0.00554

Gnomad AMR

AF:

0.0311

Gnomad ASJ

AF:

0.0348

Gnomad EAS

AF:

0.00157

Gnomad SAS

AF:

0.0483

Gnomad FIN

AF:

0.0276

Gnomad MID

AF:

0.0865

Gnomad NFE

AF:

0.0274

Gnomad OTH

AF:

0.0538

GnomAD3 exomes

AF:

0.0497

AC:

6969

AN:

140090

Hom.:

132

AF XY:

0.0508

AC XY:

3756

AN XY:

73980

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.0292

Gnomad ASJ exome

AF:

0.0536

Gnomad EAS exome

AF:

0.00372

Gnomad SAS exome

AF:

0.0697

Gnomad FIN exome

AF:

0.0424

Gnomad NFE exome

AF:

0.0475

Gnomad OTH exome

AF:

0.0543

GnomAD4 exome

AF:

0.0351

AC:

42815

AN:

1221270

Hom.:

562

AF XY:

0.0359

AC XY:

21703

AN XY:

604248

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.0267

Gnomad4 ASJ exome

AF:

0.0467

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.0587

Gnomad4 FIN exome

AF:

0.0338

Gnomad4 NFE exome

AF:

0.0318

Gnomad4 OTH exome

AF:

0.0408

GnomAD4 genome

AF:

0.0450

AC:

6764

AN:

150406

Hom.:

233

Cov.:

AF XY:

0.0446

AC XY:

3276

AN XY:

73418

show subpopulations

Gnomad4 AFR

AF:

0.0895

Gnomad4 AMR

AF:

0.0311

Gnomad4 ASJ

AF:

0.0348

Gnomad4 EAS

AF:

0.00157

Gnomad4 SAS

AF:

0.0485

Gnomad4 FIN

AF:

0.0276

Gnomad4 NFE

AF:

0.0274

Gnomad4 OTH

AF:

0.0532

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Dec 08, 2014

c.1917+13GT[10] in intron 15 of PCDH15: This variant is not expected to have cli nical significance because it is not located within the splice consensus sequenc e. It has been detected in 8.9% (4209/47276) of chromosomes across several diver se populations by the Exome Aggregate Consortium (http://exac.broadinstitute.org /variant/10-55892600-TAC-T). -

Autosomal recessive nonsyndromic hearing loss 23

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Usher syndrome type 1F

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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