10-101010536-TGCTGCGGCTGCG-TGCTGCGGCTGCGGCTGCG

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_001195263.2(PDZD7):c.2347_2352dupCGCAGC(p.Ser784_Ser785insArgSer) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,523,516 control chromosomes in the GnomAD database, including 154,616 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11806 hom., cov: 0)

Exomes 𝑓: 0.45 ( 142810 hom. )

Consequence

PDZD7
NM_001195263.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.894

Publications

10 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 10-101010536-T-TGCTGCG is Benign according to our data. Variant chr10-101010536-T-TGCTGCG is described in ClinVar as Benign. ClinVar VariationId is 44126.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2 link	c.2347_2352dupCGCAGC	p.Ser784_Ser785insArgSer	conservative_inframe_insertion	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.2347_2352dupCGCAGC	p.Ser784_Ser785insArgSer	conservative_inframe_insertion	Exon 15 of 17	5	NM_001195263.2	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000474125.7 link	n.2294_2299dupCGCAGC		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000474447.1	S4R3J9
PDZD7	ENST00000474125.7 link	n.2294_2299dupCGCAGC		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54483

AN:

151212

Hom.:

11808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.590

Gnomad AMR

AF:

0.395

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.0624

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.449

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.368

GnomAD2 exomes

AF:

0.383

AC:

49335

AN:

128718

AF XY:

0.388

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.367

Gnomad ASJ exome

AF:

0.485

Gnomad EAS exome

AF:

0.0572

Gnomad FIN exome

AF:

0.470

Gnomad NFE exome

AF:

0.474

Gnomad OTH exome

AF:

0.406

GnomAD4 exome

AF:

0.446

AC:

612106

AN:

1372190

Hom.:

142810

Cov.:

AF XY:

0.445

AC XY:

300439

AN XY:

675136

show subpopulations

African (AFR)

AF:

0.120

AC:

3756

AN:

31394

American (AMR)

AF:

0.369

AC:

13042

AN:

35310

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

12319

AN:

24584

East Asian (EAS)

AF:

0.0478

AC:

1698

AN:

35510

South Asian (SAS)

AF:

0.373

AC:

29212

AN:

78304

European-Finnish (FIN)

AF:

0.481

AC:

16118

AN:

33522

Middle Eastern (MID)

AF:

0.418

AC:

2336

AN:

5588

European-Non Finnish (NFE)

AF:

0.477

AC:

510369

AN:

1070652

Other (OTH)

AF:

0.406

AC:

23256

AN:

57326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

20099

40199

60298

80398

100497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15156

30312

45468

60624

75780

<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:

0.360

AC:

54487

AN:

151326

Hom.:

11806

Cov.:

AF XY:

0.359

AC XY:

26538

AN XY:

73868

show subpopulations

African (AFR)

AF:

0.138

AC:

5690

AN:

41342

American (AMR)

AF:

0.395

AC:

6013

AN:

15214

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

1706

AN:

3460

East Asian (EAS)

AF:

0.0625

AC:

323

AN:

5168

South Asian (SAS)

AF:

0.363

AC:

1735

AN:

4786

European-Finnish (FIN)

AF:

0.481

AC:

5015

AN:

10430

Middle Eastern (MID)

AF:

0.429

AC:

126

AN:

294

European-Non Finnish (NFE)

AF:

0.482

AC:

32581

AN:

67636

Other (OTH)

AF:

0.366

AC:

767

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1474

2948

4421

5895

7369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.351

Hom.:

1561

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Feb 05, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 05, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg783_Ser784dup in exon 15A of PDZD7: This variant is not expected to have clin ical significance because it has been identified in 27% (584/2178) of chromosome s from a broad population (1000Genomes, dbSNP rs200896335). -

Jul 22, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Usher syndrome type 2C

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hearing loss, autosomal recessive 57

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.89

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