rs373916538

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_033056.4(PCDH15):c.5278_5286delCCTGCTCCT(p.Pro1760_Pro1762del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00022 in 1,587,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1760P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

PCDH15
NM_033056.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.46

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 23
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia
Usher syndrome type 1
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 1F
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
nonsyndromic genetic hearing loss
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

PCDH15 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP6

Variant 10-53822439-CAGGAGCAGG-C is Benign according to our data. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-53822439-CAGGAGCAGG-C is described in CliVar as Likely_benign. Clinvar id is 421481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDH15	NM_033056.4 link	c.5278_5286delCCTGCTCCT	p.Pro1760_Pro1762del	conservative_inframe_deletion	Exon 33 of 33	ENST00000320301.11	NP_149045.3	Q96QU1-1
PCDH15	NM_001384140.1 link	c.4368-2218_4368-2210delCCTGCTCCT		intron_variant	Intron 32 of 37	ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11 link	c.5278_5286delCCTGCTCCT	p.Pro1760_Pro1762del	conservative_inframe_deletion	Exon 33 of 33	1	NM_033056.4	ENSP00000322604.6		Q96QU1-1
PCDH15	ENST00000644397.2 link	c.4368-2218_4368-2210delCCTGCTCCT		intron_variant	Intron 32 of 37		NM_001384140.1	ENSP00000495195.1		A0A2R8Y6C0

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

171

AN:

149610

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00407

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000400

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000313

AC:

AN:

211150

AF XY:

0.000244

show subpopulations

Gnomad AFR exome

AF:

0.00440

Gnomad AMR exome

AF:

0.000160

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000658

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000335

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.000124

AC:

178

AN:

1437614

Hom.:

AF XY:

0.000130

AC XY:

AN XY:

713570

show subpopulations

African (AFR)

AF:

0.00336

AC:

108

AN:

32106

American (AMR)

AF:

0.000215

AC:

AN:

41848

Ashkenazi Jewish (ASJ)

AF:

0.0000387

AC:

AN:

25840

East Asian (EAS)

AF:

0.000107

AC:

AN:

37430

South Asian (SAS)

AF:

0.0000477

AC:

AN:

83860

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51602

Middle Eastern (MID)

AF:

0.000712

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.0000273

AC:

AN:

1099840

Other (OTH)

AF:

0.000303

AC:

AN:

59468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00114

AC:

171

AN:

149726

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

AN XY:

73102

show subpopulations

African (AFR)

AF:

0.00406

AC:

164

AN:

40438

American (AMR)

AF:

0.000400

AC:

AN:

15010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5016

South Asian (SAS)

AF:

0.00

AC:

AN:

4734

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67462

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000569

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 23, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PCDH15: BS1 -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

Nov 03, 2017

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 25, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Pro1760_Pro1762del in exon 33 of PCDH15: This variant is not expected to have clinical significance because it has been identified in 0.4% (77/20736) of Afric an chromosomes by the Genome Aggregation Database (gnomAD, http://exac.broadinst itute.org; dbSNP rs373916538). -

PCDH15-related disorder

Benign:1

Aug 10, 2023

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Usher syndrome type 1F

Benign:1

Mar 05, 2018

Counsyl

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.5

Mutation Taster

=161/39

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over