rs397516634

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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

Publications

1 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 -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001195263.2

BP6

Variant 10-101010552-GCGGCTACGGCTGCGGCTA-G is Benign according to our data. Variant chr10-101010552-GCGGCTACGGCTGCGGCTA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2 link	c.2319_2336delTAGCCGCAGCCGTAGCCG	p.Ser774_Arg779del	disruptive_inframe_deletion	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.2319_2336delTAGCCGCAGCCGTAGCCG	p.Ser774_Arg779del	disruptive_inframe_deletion	Exon 15 of 17	5	NM_001195263.2	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000474125.7 link	n.2266_2283delTAGCCGCAGCCGTAGCCG		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000474447.1	S4R3J9
PDZD7	ENST00000474125.7 link	n.2266_2283delTAGCCGCAGCCGTAGCCG		3_prime_UTR_variant	Exon 11 of 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

GnomAD2 exomes

AF:

0.00624

AC:

818

AN:

130986

AF XY:

0.00621

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 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

African (AFR)

AF:

0.00166

AC:

AN:

31356

American (AMR)

AF:

0.00446

AC:

158

AN:

35426

Ashkenazi Jewish (ASJ)

AF:

0.00567

AC:

141

AN:

24846

East Asian (EAS)

AF:

0.000169

AC:

AN:

35474

South Asian (SAS)

AF:

0.00393

AC:

309

AN:

78622

European-Finnish (FIN)

AF:

0.00154

AC:

AN:

33676

Middle Eastern (MID)

AF:

0.0229

AC:

129

AN:

5642

European-Non Finnish (NFE)

AF:

0.0119

AC:

12762

AN:

1070732

Other (OTH)

AF:

0.00943

AC:

541

AN:

57376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

Heterozygous variant carriers

946

1891

2837

3782

4728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

512

1024

1536

2048

2560

<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

AF:

0.00673

AC:

1021

AN:

151680

Hom.:

Cov.:

AF XY:

0.00643

AC XY:

477

AN XY:

74142

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41412

American (AMR)

AF:

0.00806

AC:

123

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3466

East Asian (EAS)

AF:

0.00116

AC:

AN:

5166

South Asian (SAS)

AF:

0.00418

AC:

AN:

4786

European-Finnish (FIN)

AF:

0.000757

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0110

AC:

746

AN:

67720

Other (OTH)

AF:

0.00857

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

102

154

205

256

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:

0.00527

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

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PDZD7: BS1, BS2 -

Sep 13, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27068579) -

Nov 26, 2018

Athena Diagnostics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Mar 09, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Feb 20, 2015

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PDZD7-related disorder

Benign:1

Nov 30, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

PhyloP100

2.4

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