rs34705415

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1011C>T(p.Tyr337Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,546,464 control chromosomes in the GnomAD database, including 372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 24 hom., cov: 32)

Exomes 𝑓: 0.010 ( 348 hom. )

Consequence

PDZD7
NM_001195263.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.537

Publications

6 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=-0.8).

BP6

Variant 10-101019135-G-A is Benign according to our data. Variant chr10-101019135-G-A is described in ClinVar as Benign. ClinVar VariationId is 46206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.537 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2 link	c.1011C>T	p.Tyr337Tyr	synonymous_variant	Exon 8 of 17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZD7	ENST00000619208.6 link	c.1011C>T	p.Tyr337Tyr	synonymous_variant	Exon 8 of 17	5	NM_001195263.2	ENSP00000480489.1

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1533

AN:

152274

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00651

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0197

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.0192

Gnomad SAS

AF:

0.0722

Gnomad FIN

AF:

0.000658

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00591

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.0241

AC:

3558

AN:

147572

AF XY:

0.0270

show subpopulations

Gnomad AFR exome

AF:

0.00749

Gnomad AMR exome

AF:

0.0369

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.0196

Gnomad FIN exome

AF:

0.000637

Gnomad NFE exome

AF:

0.00647

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.0101

AC:

14102

AN:

1394072

Hom.:

348

Cov.:

AF XY:

0.0122

AC XY:

8398

AN XY:

689050

show subpopulations

African (AFR)

AF:

0.00718

AC:

232

AN:

32324

American (AMR)

AF:

0.0335

AC:

1234

AN:

36864

Ashkenazi Jewish (ASJ)

AF:

0.0154

AC:

388

AN:

25198

East Asian (EAS)

AF:

0.0127

AC:

467

AN:

36756

South Asian (SAS)

AF:

0.0748

AC:

5977

AN:

79952

European-Finnish (FIN)

AF:

0.000685

AC:

AN:

35042

Middle Eastern (MID)

AF:

0.0378

AC:

202

AN:

5338

European-Non Finnish (NFE)

AF:

0.00442

AC:

4796

AN:

1084380

Other (OTH)

AF:

0.0134

AC:

782

AN:

58218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

978

1955

2933

3910

4888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

224

448

672

896

1120

<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:

0.0101

AC:

1533

AN:

152392

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

832

AN XY:

74520

show subpopulations

African (AFR)

AF:

0.00651

AC:

271

AN:

41602

American (AMR)

AF:

0.0199

AC:

305

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3472

East Asian (EAS)

AF:

0.0191

AC:

AN:

5184

South Asian (SAS)

AF:

0.0717

AC:

346

AN:

4828

European-Finnish (FIN)

AF:

0.000658

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00589

AC:

401

AN:

68042

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

164

245

327

409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00664

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

Dec 17, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Jul 30, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Tyr337Tyr 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 0.8% (53/6688) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs34705415). -

Usher syndrome type 2A;C2931213:Usher syndrome type 2C;C4693893:Hearing loss, autosomal recessive 57

Benign:1

Oct 18, 2021

Fulgent Genetics, Fulgent Genetics

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

-0.80

CADD

Benign

4.7

(source)

DANN

Benign

0.94

PhyloP100

0.54

Mutation Taster

=100/0

polymorphism (auto)

(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

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