Variant 10-54132840-TACACACAC-TACACACACAC 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+34dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,470,580 control chromosomes in the GnomAD database, including 7,105 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 1897 hom., cov: 0)

Exomes 𝑓: 0.14 ( 5208 hom. )

Consequence

PCDH15
NM_001384140.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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-T-TAC is Benign according to our data. Variant chr10-54132840-T-TAC is described in ClinVar as [Benign]. Clinvar id is 227007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 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+34dupGT		intron_variant		ENST00000320301.11	NP_149045.3	Q96QU1-1
PCDH15	NM_001384140.1 linkuse as main transcript	c.1917+33_1917+34dupGT		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+34dupGT		intron_variant		1	NM_033056.4	ENSP00000322604.6		Q96QU1-1
PCDH15	ENST00000644397.2 linkuse as main transcript	c.1917+33_1917+34dupGT		intron_variant			NM_001384140.1	ENSP00000495195.1		A0A2R8Y6C0

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23468

AN:

150306

Hom.:

1894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.224

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0878

Gnomad MID

AF:

0.119

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.168

GnomAD3 exomes

AF:

0.198

AC:

27706

AN:

140090

Hom.:

985

AF XY:

0.191

AC XY:

14101

AN XY:

73980

show subpopulations

Gnomad AFR exome

AF:

0.214

Gnomad AMR exome

AF:

0.312

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.342

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.126

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.137

AC:

180874

AN:

1320168

Hom.:

5208

Cov.:

AF XY:

0.136

AC XY:

89074

AN XY:

653880

show subpopulations

Gnomad4 AFR exome

AF:

0.186

Gnomad4 AMR exome

AF:

0.245

Gnomad4 ASJ exome

AF:

0.140

Gnomad4 EAS exome

AF:

0.339

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.0982

Gnomad4 NFE exome

AF:

0.129

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.156

AC:

23497

AN:

150412

Hom.:

1897

Cov.:

AF XY:

0.156

AC XY:

11459

AN XY:

73422

show subpopulations

Gnomad4 AFR

AF:

0.193

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.288

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.0878

Gnomad4 NFE

AF:

0.128

Gnomad4 OTH

AF:

0.171

ClinVar

Significance: Benign

Submissions summary: Benign:2

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[12] 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 17.5% (8259/47276) of chromosomes across several dive rse populations by the Exome Aggregate Consortium (http://exac.broadinstitute.or g/variant/10-55892600-T-TAC). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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