rs143414291

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 9/12 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 44123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101010745-G-A is described in Lovd as [Likely_benign]. Variant chr10-101010745-G-A is described in Lovd as [Benign].

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	Q9H5P4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDZD7	ENST00000619208.6 link	c.2144C>T	p.Pro715Leu	missense_variant	Exon 15 of 17	5	NM_001195263.2	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000474125.7 link	n.*2091C>T		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000474447.1	S4R3J9
PDZD7	ENST00000474125.7 link	n.*2091C>T		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1168

AN:

145922

Hom.:

Cov.:

FAILED QC

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

GnomAD3 exomes

AF:

0.00750

AC:

974

AN:

129826

Hom.:

AF XY:

0.00717

AC XY:

510

AN XY:

71156

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 SAS exome

AF:

0.00308

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

Gnomad4 AFR exome

AF:

0.00168

Gnomad4 AMR exome

AF:

0.00775

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0000488

Gnomad4 SAS exome

AF:

0.00303

Gnomad4 FIN exome

AF:

0.0222

Gnomad4 NFE exome

AF:

0.0118

Gnomad4 OTH exome

AF:

0.0119

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

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.0123

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00298

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.0106

Gnomad4 OTH

AF:

0.0122

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

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

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 31, 2018

Athena Diagnostics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PDZD7: BP4, BS1 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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) -

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). -

Jan 23, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

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

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

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