NM_001195263.2:c.1008C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B.

-20

BP4_StrongBP6_Very_StrongBS1BS2

The NM_001195263.2(PDZD7):c.1008C>T(p.Pro336Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00823 in 1,545,728 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P336P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0070 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0084 ( 57 hom. )

Consequence

PDZD7
NM_001195263.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.24

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 10-101019138-G-A is Benign according to our data. Variant chr10-101019138-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178525.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 = 0.00696 (1061/152388) while in subpopulation NFE AF = 0.00961 (654/68036). AF 95% confidence interval is 0.009. There are 4 homozygotes in GnomAd4. There are 534 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2 link	c.1008C>T	p.Pro336Pro	synonymous_variant	Exon 8 of 17	ENST00000619208.6	NP_001182192.1	Q9H5P4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6 link	c.1008C>T	p.Pro336Pro	synonymous_variant	Exon 8 of 17	5	NM_001195263.2	ENSP00000480489.1		Q9H5P4-3

Frequencies

GnomAD3 genomes

AF:

0.00697

AC:

1061

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00837

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00961

Gnomad OTH

AF:

0.00765

GnomAD2 exomes

AF:

0.00629

AC:

926

AN:

147152

AF XY:

0.00629

show subpopulations

Gnomad AFR exome

AF:

0.00128

Gnomad AMR exome

AF:

0.00495

Gnomad ASJ exome

AF:

0.00651

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00867

Gnomad NFE exome

AF:

0.00992

Gnomad OTH exome

AF:

0.00769

GnomAD4 exome

AF:

0.00837

AC:

11658

AN:

1393340

Hom.:

Cov.:

AF XY:

0.00821

AC XY:

5654

AN XY:

688628

show subpopulations

African (AFR)

AF:

0.00130

AC:

AN:

32282

American (AMR)

AF:

0.00497

AC:

183

AN:

36804

Ashkenazi Jewish (ASJ)

AF:

0.00727

AC:

183

AN:

25186

East Asian (EAS)

AF:

0.00

AC:

AN:

36712

South Asian (SAS)

AF:

0.00267

AC:

213

AN:

79888

European-Finnish (FIN)

AF:

0.00752

AC:

263

AN:

34954

Middle Eastern (MID)

AF:

0.00504

AC:

AN:

5358

European-Non Finnish (NFE)

AF:

0.00956

AC:

10358

AN:

1083954

Other (OTH)

AF:

0.00668

AC:

389

AN:

58202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

868

1736

2605

3473

4341

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.00696

AC:

1061

AN:

152388

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

534

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

41602

American (AMR)

AF:

0.00836

AC:

128

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00269

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0123

AC:

131

AN:

10630

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00961

AC:

654

AN:

68036

Other (OTH)

AF:

0.00757

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

108

163

217

271

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:

0.00470

Hom.:

Bravo

AF:

0.00628

Asia WGS

AF:

0.00115

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

Dec 18, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PDZD7: BP4, BP7, BS2 -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 06, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Pro336Pro in Exon 08 of PDZD7: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.5% (35/6694) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs144469613). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 09, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

1.2

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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