Variant rs727503363 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong

The NM_033056.4(PCDH15):c.5269_5277delTCTCCTCCT(p.Ser1757_Pro1759del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00058 in 1,597,072 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 0 hom. )

Consequence

PCDH15
NM_033056.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.32

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:

PCDH15 (HGNC:):

PCDH15 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 10-53822448-GAGGAGGAGA-G is Benign according to our data. Variant chr10-53822448-GAGGAGGAGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 164903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_033056.4 linkuse as main transcript	c.5269_5277delTCTCCTCCT	p.Ser1757_Pro1759del	conservative_inframe_deletion	33/33	ENST00000320301.11	NP_149045.3	Q96QU1-1
PCDH15	NM_001384140.1 linkuse as main transcript	c.4368-2227_4368-2219delTCTCCTCCT		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.5269_5277delTCTCCTCCT	p.Ser1757_Pro1759del	conservative_inframe_deletion	33/33	1	NM_033056.4	ENSP00000322604.6		Q96QU1-1
PCDH15	ENST00000644397.2 linkuse as main transcript	c.4368-2227_4368-2219delTCTCCTCCT		intron_variant			NM_001384140.1	ENSP00000495195.1		A0A2R8Y6C0

Frequencies

GnomAD3 genomes

AF:

0.000298

AC:

AN:

151224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000343

AC:

AN:

221474

Hom.:

AF XY:

0.000357

AC XY:

AN XY:

120456

show subpopulations

Gnomad AFR exome

AF:

0.000301

Gnomad AMR exome

AF:

0.0000615

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000124

Gnomad SAS exome

AF:

0.0000697

Gnomad FIN exome

AF:

0.0000492

Gnomad NFE exome

AF:

0.000630

Gnomad OTH exome

AF:

0.000887

GnomAD4 exome

AF:

0.000609

AC:

881

AN:

1445732

Hom.:

AF XY:

0.000581

AC XY:

417

AN XY:

718148

show subpopulations

Gnomad4 AFR exome

AF:

0.000650

Gnomad4 AMR exome

AF:

0.0000697

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000157

Gnomad4 SAS exome

AF:

0.0000946

Gnomad4 FIN exome

AF:

0.0000577

Gnomad4 NFE exome

AF:

0.000706

Gnomad4 OTH exome

AF:

0.00102

GnomAD4 genome

AF:

0.000297

AC:

AN:

151340

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

73978

show subpopulations

Gnomad4 AFR

AF:

0.000294

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000348

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 29, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 16, 2013

Ser1757_Pro1759del in exon 33 of PCDH15: This variant is not expected to have c linical significance because it has been identified in 0.12% (10/8244) of Europe an American chromosomes and 0.58% (25/4260) of African American chromosomes by t he NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/) -

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