rs143414291

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001195263.2(PDZD7):c.2144C>T(p.Pro715Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 10 hom., cov: 29)

Exomes 𝑓: 0.011 ( 80 hom. )

Failed GnomAD Quality Control

Consequence

PDZD7
NM_001195263.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.25

Publications

5 publications found

Variant links:

Genes affected

PDZD7 (HGNC:26257): (PDZ domain containing 7) This gene encodes a ciliary protein homologous to proteins which are mutated in Usher syndrome patients, and mutations and translocations involving this gene have been associated with two types of Usher syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

PDZD7 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive 57
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
Usher syndrome type 2C
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

PDZD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062847733).

BP6

Variant 10-101010745-G-A is Benign according to our data. Variant chr10-101010745-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44123.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
PDZD7	NM_001195263.2 link	c.2144C>T	p.Pro715Leu	missense_variant	Exon 15 of 17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PDZD7	ENST00000619208.6 link	c.2144C>T	p.Pro715Leu	missense_variant	Exon 15 of 17	5	NM_001195263.2	ENSP00000480489.1
PDZD7	ENST00000474125.7 link	n.*2091C>T		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000474447.1
PDZD7	ENST00000474125.7 link	n.*2091C>T		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000474447.1

Frequencies

GnomAD3 genomes

AF:

0.00800

AC:

1168

AN:

145922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00454

Gnomad AMR

AF:

0.0123

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00321

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.00974

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.0123

GnomAD2 exomes

AF:

0.00750

AC:

974

AN:

129826

AF XY:

0.00717

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.00600

Gnomad ASJ exome

AF:

0.0147

Gnomad EAS exome

AF:

0.0000959

Gnomad FIN exome

AF:

0.0122

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00769

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0110

AC:

12944

AN:

1181656

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

6291

AN XY:

584122

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

26822

American (AMR)

AF:

0.00775

AC:

242

AN:

31230

Ashkenazi Jewish (ASJ)

AF:

0.0189

AC:

359

AN:

18998

East Asian (EAS)

AF:

0.0000488

AC:

AN:

20484

South Asian (SAS)

AF:

0.00303

AC:

232

AN:

76664

European-Finnish (FIN)

AF:

0.0222

AC:

436

AN:

19606

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

4856

European-Non Finnish (NFE)

AF:

0.0118

AC:

11024

AN:

936860

Other (OTH)

AF:

0.0119

AC:

550

AN:

46136

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.608

Heterozygous variant carriers

606

1211

1817

2422

3028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

406

812

1218

1624

2030

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00800

AC:

1168

AN:

146054

Hom.:

Cov.:

AF XY:

0.00803

AC XY:

571

AN XY:

71112

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

40008

American (AMR)

AF:

0.0123

AC:

179

AN:

14596

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3400

East Asian (EAS)

AF:

0.00

AC:

AN:

4712

South Asian (SAS)

AF:

0.00298

AC:

AN:

4360

European-Finnish (FIN)

AF:

0.0118

AC:

113

AN:

9568

Middle Eastern (MID)

AF:

0.0140

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0106

AC:

700

AN:

66192

Other (OTH)

AF:

0.0122

AC:

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.591

Heterozygous variant carriers

106

160

213

266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0101

Hom.:

Bravo

AF:

0.00798

ExAC

AF:

0.00492

AC:

108

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:6

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 31, 2018

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 20, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 24498627) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PDZD7: BP4, BS1 -

not specified

Benign:3

Jan 25, 2018

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Pro715Leu in exon 15 of PDZD7: This variant is not expected to have clinical s ignificance because it has been identified in 4.3% (10/230) of Hispanic chromoso mes from the 1000 Genomes project (http://www.ncbi.nlm.nih.gov/variation/tools/1 000genomes; rs143414291). -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 23, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.79

Eigen

Benign

-0.042

Eigen_PC

Benign

0.031

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.63

.;T

MetaRNN

Benign

0.0063

T;T

MetaSVM

Benign

-0.99

PhyloP100

3.2

PrimateAI

Benign

0.47

Sift4G

Uncertain

0.021

.;D

Vest4

0.17

MVP

0.093

ClinPred

0.094

GERP RS

3.5

Varity_R

0.066

gMVP

0.37

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