NM_001195263.2:c.2049G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001195263.2(PDZD7):c.2049G>A(p.Pro683Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,534,700 control chromosomes in the GnomAD database, including 1,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 461 hom., cov: 31)

Exomes 𝑓: 0.033 ( 1093 hom. )

Consequence

PDZD7
NM_001195263.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -6.41

Publications

3 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 10-101010840-C-T is Benign according to our data. Variant chr10-101010840-C-T is described in ClinVar as Benign. ClinVar VariationId is 44120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.41 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2 link	c.2049G>A	p.Pro683Pro	synonymous_variant	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.2049G>A	p.Pro683Pro	synonymous_variant	Exon 15 of 17	5	NM_001195263.2	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000474125.7 link	n.*1996G>A		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000474447.1	S4R3J9
PDZD7	ENST00000474125.7 link	n.*1996G>A		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000474447.1	S4R3J9
PDZD7	ENST00000644782.1 link	c.*942G>A		downstream_gene_variant				ENSP00000496747.1	A0A2R8Y892

Frequencies

GnomAD3 genomes

AF:

0.0595

AC:

9046

AN:

152032

Hom.:

460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0314

Gnomad ASJ

AF:

0.0573

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0383

Gnomad FIN

AF:

0.0458

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0266

Gnomad OTH

AF:

0.0551

GnomAD2 exomes

AF:

0.0360

AC:

4737

AN:

131732

AF XY:

0.0364

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.0234

Gnomad ASJ exome

AF:

0.0525

Gnomad EAS exome

AF:

0.0000958

Gnomad FIN exome

AF:

0.0505

Gnomad NFE exome

AF:

0.0279

Gnomad OTH exome

AF:

0.0326

GnomAD4 exome

AF:

0.0335

AC:

46248

AN:

1382550

Hom.:

1093

Cov.:

AF XY:

0.0335

AC XY:

22851

AN XY:

682158

show subpopulations

African (AFR)

AF:

0.143

AC:

4516

AN:

31558

American (AMR)

AF:

0.0245

AC:

875

AN:

35696

Ashkenazi Jewish (ASJ)

AF:

0.0514

AC:

1295

AN:

25182

East Asian (EAS)

AF:

0.0000840

AC:

AN:

35734

South Asian (SAS)

AF:

0.0441

AC:

3496

AN:

79194

European-Finnish (FIN)

AF:

0.0471

AC:

1578

AN:

33470

Middle Eastern (MID)

AF:

0.0394

AC:

198

AN:

5022

European-Non Finnish (NFE)

AF:

0.0298

AC:

32121

AN:

1078884

Other (OTH)

AF:

0.0375

AC:

2166

AN:

57810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

2773

5546

8318

11091

13864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1326

2652

3978

5304

6630

<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:

0.0596

AC:

9065

AN:

152150

Hom.:

461

Cov.:

AF XY:

0.0584

AC XY:

4346

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.139

AC:

5766

AN:

41448

American (AMR)

AF:

0.0313

AC:

479

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0573

AC:

199

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5178

South Asian (SAS)

AF:

0.0383

AC:

185

AN:

4832

European-Finnish (FIN)

AF:

0.0458

AC:

485

AN:

10588

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0266

AC:

1812

AN:

68016

Other (OTH)

AF:

0.0545

AC:

115

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

399

798

1197

1596

1995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0340

Hom.:

260

Bravo

AF:

0.0623

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jun 02, 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. -

May 24, 2018

Athena Diagnostics

Significance: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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Pro683Pro in Exon 15 of PDZD7: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 12.7% (15/118) of ch romosomes from a population in the dbSNP database (http://www.ncbi.nlm.nih.gov/p rojects/SNP; rs34693310). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.046

(source)

DANN

Benign

0.71

PhyloP100

-6.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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