10-54132840-TACACACACACAC-TACACACACAC

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_033056.4(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_033056.4 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: -0.0900

Publications

2 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 -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 VariationId is 227006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PCDH15	NM_033056.4 link	c.1917+33_1917+34delGT		intron_variant	Intron 15 of 32	ENST00000320301.11	NP_149045.3	Q96QU1-1
PCDH15	NM_001384140.1 link	c.1917+33_1917+34delGT		intron_variant	Intron 15 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.1917+33_1917+34delGT		intron_variant	Intron 15 of 32	1	NM_033056.4	ENSP00000322604.6		Q96QU1-1
PCDH15	ENST00000644397.2 link	c.1917+33_1917+34delGT		intron_variant	Intron 15 of 37		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

GnomAD2 exomes

AF:

0.0497

AC:

6969

AN:

140090

AF XY:

0.0508

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 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

African (AFR)

AF:

0.109

AC:

3037

AN:

27934

American (AMR)

AF:

0.0267

AC:

892

AN:

33430

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

973

AN:

20822

East Asian (EAS)

AF:

0.00134

AC:

AN:

34262

South Asian (SAS)

AF:

0.0587

AC:

4136

AN:

70456

European-Finnish (FIN)

AF:

0.0338

AC:

1469

AN:

43424

Middle Eastern (MID)

AF:

0.0825

AC:

417

AN:

5054

European-Non Finnish (NFE)

AF:

0.0318

AC:

29774

AN:

935136

Other (OTH)

AF:

0.0408

AC:

2071

AN:

50752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.424

Heterozygous variant carriers

1862

3724

5585

7447

9309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1094

2188

3282

4376

5470

<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:

0.0450

AC:

6764

AN:

150406

Hom.:

233

Cov.:

AF XY:

0.0446

AC XY:

3276

AN XY:

73418

show subpopulations

African (AFR)

AF:

0.0895

AC:

3666

AN:

40960

American (AMR)

AF:

0.0311

AC:

469

AN:

15102

Ashkenazi Jewish (ASJ)

AF:

0.0348

AC:

120

AN:

3444

East Asian (EAS)

AF:

0.00157

AC:

AN:

5082

South Asian (SAS)

AF:

0.0485

AC:

231

AN:

4760

European-Finnish (FIN)

AF:

0.0276

AC:

284

AN:

10308

Middle Eastern (MID)

AF:

0.0822

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0274

AC:

1846

AN:

67470

Other (OTH)

AF:

0.0532

AC:

111

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

295

591

886

1182

1477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<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:

0.0649

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 08, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 1F

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Aug 08, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.090

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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