rs112571971

Positions:

chr10-101015772-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001195263.2(PDZD7):c.1613G>A(p.Gly538Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00675 in 1,549,712 control chromosomes in the GnomAD database, including 63 homozygotes. 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 0.0066 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 54 hom. )

Consequence

PDZD7
NM_001195263.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.908

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003160268).

BP6

Variant 10-101015772-C-T is Benign according to our data. Variant chr10-101015772-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 44119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101015772-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00661 (1006/152264) while in subpopulation NFE AF= 0.00778 (529/68008). AF 95% confidence interval is 0.00723. There are 9 homozygotes in gnomad4. There are 541 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD7	NM_001195263.2 linkuse as main transcript	c.1613G>A	p.Gly538Glu	missense_variant	11/17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6 linkuse as main transcript	c.1613G>A	p.Gly538Glu	missense_variant	11/17	5	NM_001195263.2	ENSP00000480489	P1	Q9H5P4-3
PDZD7	ENST00000644782.1 linkuse as main transcript	c.1522+2327G>A		intron_variant				ENSP00000496747
PDZD7	ENST00000474125.7 linkuse as main transcript	c.*1700+2327G>A		intron_variant, NMD_transcript_variant		2		ENSP00000474447

Frequencies

GnomAD3 genomes

AF:

0.00661

AC:

1006

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00563

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0305

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00778

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00695

AC:

1018

AN:

146564

Hom.:

AF XY:

0.00692

AC XY:

547

AN XY:

79058

show subpopulations

Gnomad AFR exome

AF:

0.000296

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00216

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000311

Gnomad FIN exome

AF:

0.0319

Gnomad NFE exome

AF:

0.00736

Gnomad OTH exome

AF:

0.00755

GnomAD4 exome

AF:

0.00676

AC:

9447

AN:

1397448

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

4535

AN XY:

689254

show subpopulations

Gnomad4 AFR exome

AF:

0.000570

Gnomad4 AMR exome

AF:

0.00275

Gnomad4 ASJ exome

AF:

0.00207

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.000581

Gnomad4 FIN exome

AF:

0.0309

Gnomad4 NFE exome

AF:

0.00692

Gnomad4 OTH exome

AF:

0.00477

GnomAD4 genome

AF:

0.00661

AC:

1006

AN:

152264

Hom.:

Cov.:

AF XY:

0.00727

AC XY:

541

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.0305

Gnomad4 NFE

AF:

0.00778

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00638

Hom.:

Bravo

AF:

0.00406

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00649

AC:

ExAC

AF:

0.00178

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 18, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 22, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	PDZD7: BP4, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 05, 2013	Gly538Glu in Exon 11 of PDZD7: This variant is not expected to have clinical sig nificance because it has been identified in 1.6% (3/186) of Finnish individuals from a broad population by the 1000 Genomes Project (rs112571971). -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 28, 2015	- -

PDZD7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 18, 2019

This variant is classified as 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

0.11

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.71

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.54

.;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.32

Sift4G

Benign

0.95

.;T

Vest4

0.056

MVP

0.043

ClinPred

0.013

GERP RS

3.0

Varity_R

0.059

gMVP

0.39

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