rs397516634

Positions:

chr10-101010552-GCGGCTACGGCTGCGGCTA-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001195263.2(PDZD7):c.2319_2336delTAGCCGCAGCCGTAGCCG(p.Ser774_Arg779del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00995 in 1,524,830 control chromosomes in the GnomAD database, including 120 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R773R) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0067 ( 5 hom., cov: 28)

Exomes 𝑓: 0.010 ( 115 hom. )

Consequence

PDZD7
NM_001195263.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.36

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 -16 ACMG points.

BP6

Variant 10-101010552-GCGGCTACGGCTGCGGCTA-G is Benign according to our data. Variant chr10-101010552-GCGGCTACGGCTGCGGCTA-G is described in ClinVar as [Likely_benign]. Clinvar id is 44125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101010552-GCGGCTACGGCTGCGGCTA-G is described in Lovd as [Likely_benign]. Variant chr10-101010552-GCGGCTACGGCTGCGGCTA-G is described in Lovd as [Likely_pathogenic].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00673 (1021/151680) while in subpopulation NFE AF= 0.011 (746/67720). AF 95% confidence interval is 0.0104. There are 5 homozygotes in gnomad4. There are 477 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD7	NM_001195263.2 linkuse as main transcript	c.2319_2336delTAGCCGCAGCCGTAGCCG	p.Ser774_Arg779del	disruptive_inframe_deletion	15/17	ENST00000619208.6	NP_001182192.1	Q9H5P4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PDZD7	ENST00000619208.6 linkuse as main transcript	c.2319_2336delTAGCCGCAGCCGTAGCCG	p.Ser774_Arg779del	disruptive_inframe_deletion	15/17	5	NM_001195263.2	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000474125.7 linkuse as main transcript	n.2266_2283delTAGCCGCAGCCGTAGCCG		non_coding_transcript_exon_variant	11/13	2		ENSP00000474447.1	S4R3J9
PDZD7	ENST00000474125.7 linkuse as main transcript	n.2266_2283delTAGCCGCAGCCGTAGCCG		3_prime_UTR_variant	11/13	2		ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes

AF:

0.00674

AC:

1021

AN:

151560

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00201

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00807

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00418

Gnomad FIN

AF:

0.000757

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.00866

GnomAD3 exomes

AF:

0.00624

AC:

818

AN:

130986

Hom.:

AF XY:

0.00621

AC XY:

442

AN XY:

71130

show subpopulations

Gnomad AFR exome

AF:

0.000779

Gnomad AMR exome

AF:

0.00404

Gnomad ASJ exome

AF:

0.00521

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.00325

Gnomad FIN exome

AF:

0.00118

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00863

GnomAD4 exome

AF:

0.0103

AC:

14150

AN:

1373150

Hom.:

115

AF XY:

0.0101

AC XY:

6813

AN XY:

676036

show subpopulations

Gnomad4 AFR exome

AF:

0.00166

Gnomad4 AMR exome

AF:

0.00446

Gnomad4 ASJ exome

AF:

0.00567

Gnomad4 EAS exome

AF:

0.000169

Gnomad4 SAS exome

AF:

0.00393

Gnomad4 FIN exome

AF:

0.00154

Gnomad4 NFE exome

AF:

0.0119

Gnomad4 OTH exome

AF:

0.00943

GnomAD4 genome

AF:

0.00673

AC:

1021

AN:

151680

Hom.:

Cov.:

AF XY:

0.00643

AC XY:

477

AN XY:

74142

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00806

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00418

Gnomad4 FIN

AF:

0.000757

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.00857

Alfa

AF:

0.00527

Hom.:

Bravo

AF:

0.00709

Asia WGS

AF:

0.00116

AC:

AN:

3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	PDZD7: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 13, 2019	This variant is associated with the following publications: (PMID: 27068579) -
Likely benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 26, 2018	- -

not specified

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 09, 2013	The Arg779_Ser784del variant in PDZD7 has not been reported in the literature no r previously identified by our laboratory.The frequency of this variant in large European American and African American populations sequenced by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/) was not reported becaus e coverage at this position was insufficient or unavailable. This in-frame delet ion lies in a variable Arg-Ser repeat region that is not conserved in species in cluding other primates. Furthermore, there is inconclusive evidence as to the ro le of the PDZD7 gene in hearing loss with only one case report suggesting PDZD7 could cause nonsyndromic hearing loss based upon a patient with a homozygous tra nslocation that disrupts the long alternate isoform of PDZD7 (Schneider 2009). I n summary, this variant is likely benign based on its presence in a variable rep eat region, lack of conservation across species, and limited evidence supporting a role of PDZD7 in hearing loss. -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 20, 2015	- -

PDZD7-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 30, 2020

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

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