NM_001195263.2:c.971G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001195263.2(PDZD7):c.971G>A(p.Ser324Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0025 in 1,537,280 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 10 hom. )

Consequence

PDZD7
NM_001195263.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:4

Conservation

PhyloP100: 4.45

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008763999).

BP6

Variant 10-101019175-C-T is Benign according to our data. Variant chr10-101019175-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 164942.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=3}.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00171 (261/152394) while in subpopulation NFE AF= 0.00295 (201/68040). AF 95% confidence interval is 0.00262. There are 1 homozygotes in gnomad4. There are 111 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 10 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2 link	c.971G>A	p.Ser324Asn	missense_variant	Exon 8 of 17	ENST00000619208.6	NP_001182192.1	Q9H5P4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6 link	c.971G>A	p.Ser324Asn	missense_variant	Exon 8 of 17	5	NM_001195263.2	ENSP00000480489.1		Q9H5P4-3

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

261

AN:

152276

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00295

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00181

AC:

250

AN:

137828

Hom.:

AF XY:

0.00202

AC XY:

151

AN XY:

74582

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.000121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00262

Gnomad FIN exome

AF:

0.000727

Gnomad NFE exome

AF:

0.00277

Gnomad OTH exome

AF:

0.000715

GnomAD4 exome

AF:

0.00259

AC:

3588

AN:

1384886

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

1769

AN XY:

683508

show subpopulations

Gnomad4 AFR exome

AF:

0.000252

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.000159

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00278

Gnomad4 FIN exome

AF:

0.00141

Gnomad4 NFE exome

AF:

0.00288

Gnomad4 OTH exome

AF:

0.00252

GnomAD4 genome

AF:

0.00171

AC:

261

AN:

152394

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.00295

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00245

Hom.:

Bravo

AF:

0.00173

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000255

AC:

ESP6500EA

AF:

0.00177

AC:

ExAC

AF:

0.00115

AC:

111

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:3Benign:3

Sep 30, 2019

Athena Diagnostics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Identified previously in a patient with retinitis pigmentosa; however, the patient harbored multiple variants in other genes and the S324N variant was not noted to segregate with disease in the family (Borrs et al., 2013); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23534816) -

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

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Uncertain:1

Aug 16, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant classified as Uncertain Significance - Favor Benign. -

PDZD7-related disorder

Benign:1

May 15, 2022

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

T;T;.;.;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.82

.;T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.0088

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;M;.;M;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.3

.;.;.;N;.

REVEL

Benign

0.088

Sift

Uncertain

0.0020

.;.;.;D;.

Sift4G

Uncertain

0.0060

.;D;.;D;.

Polyphen

1.0

D;D;.;.;.

Vest4

0.25, 0.19

MVP

0.33

MPC

0.77

ClinPred

0.068

GERP RS

4.3

Varity_R

0.25

gMVP

0.49

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

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