rs34616847

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001195263.2(PDZD7):c.2132A>G(p.His711Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 1,319,644 control chromosomes in the GnomAD database, including 720 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 82 hom., cov: 30)

Exomes 𝑓: 0.033 ( 638 hom. )

Consequence

PDZD7
NM_001195263.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.42

Publications

5 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 (MetaRNN=0.002282381).

BP6

Variant 10-101010757-T-C is Benign according to our data. Variant chr10-101010757-T-C is described in ClinVar as Benign. ClinVar VariationId is 44122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0295 (4119/139684) while in subpopulation AFR AF = 0.0357 (1342/37610). AF 95% confidence interval is 0.0341. There are 82 homozygotes in GnomAd4. There are 1978 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 82 AR,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2 link	c.2132A>G	p.His711Arg	missense_variant	Exon 15 of 17	ENST00000619208.6	NP_001182192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PDZD7	ENST00000619208.6 link	c.2132A>G	p.His711Arg	missense_variant	Exon 15 of 17	5	NM_001195263.2	ENSP00000480489.1
PDZD7	ENST00000474125.7 link	n.*2079A>G		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000474447.1
PDZD7	ENST00000474125.7 link	n.*2079A>G		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000474447.1

Frequencies

GnomAD3 genomes

AF:

0.0294

AC:

4110

AN:

139592

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0356

Gnomad AMI

AF:

0.0144

Gnomad AMR

AF:

0.0196

Gnomad ASJ

AF:

0.0603

Gnomad EAS

AF:

0.000223

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.0486

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0262

Gnomad OTH

AF:

0.0369

GnomAD2 exomes

AF:

0.0256

AC:

3330

AN:

130090

AF XY:

0.0259

show subpopulations

Gnomad AFR exome

AF:

0.0362

Gnomad AMR exome

AF:

0.0160

Gnomad ASJ exome

AF:

0.0524

Gnomad EAS exome

AF:

0.0000958

Gnomad FIN exome

AF:

0.0504

Gnomad NFE exome

AF:

0.0265

Gnomad OTH exome

AF:

0.0272

GnomAD4 exome

AF:

0.0334

AC:

39455

AN:

1179960

Hom.:

638

Cov.:

AF XY:

0.0333

AC XY:

19370

AN XY:

581500

show subpopulations

African (AFR)

AF:

0.0432

AC:

1170

AN:

27090

American (AMR)

AF:

0.0191

AC:

586

AN:

30608

Ashkenazi Jewish (ASJ)

AF:

0.0685

AC:

1294

AN:

18900

East Asian (EAS)

AF:

0.000173

AC:

AN:

17342

South Asian (SAS)

AF:

0.0275

AC:

2118

AN:

76890

European-Finnish (FIN)

AF:

0.0877

AC:

1572

AN:

17926

Middle Eastern (MID)

AF:

0.0312

AC:

146

AN:

4682

European-Non Finnish (NFE)

AF:

0.0329

AC:

30976

AN:

940870

Other (OTH)

AF:

0.0348

AC:

1590

AN:

45652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1906

3811

5717

7622

9528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1224

2448

3672

4896

6120

<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:

0.0295

AC:

4119

AN:

139684

Hom.:

Cov.:

AF XY:

0.0292

AC XY:

1978

AN XY:

67834

show subpopulations

African (AFR)

AF:

0.0357

AC:

1342

AN:

37610

American (AMR)

AF:

0.0195

AC:

277

AN:

14172

Ashkenazi Jewish (ASJ)

AF:

0.0603

AC:

199

AN:

3300

East Asian (EAS)

AF:

0.000223

AC:

AN:

4480

South Asian (SAS)

AF:

0.0253

AC:

104

AN:

4110

European-Finnish (FIN)

AF:

0.0486

AC:

428

AN:

8812

Middle Eastern (MID)

AF:

0.0172

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0262

AC:

1679

AN:

64100

Other (OTH)

AF:

0.0365

AC:

AN:

1974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

179

358

537

716

895

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0272

Hom.:

Bravo

AF:

0.0266

TwinsUK

AF:

0.0302

AC:

112

ALSPAC

AF:

0.0278

AC:

107

ExAC

AF:

0.0184

AC:

400

Asia WGS

AF:

0.0140

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

Jan 09, 2019

GeneDx

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

- -

May 29, 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

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 19, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

His711Arg in exon 15 of PDZD7: This variant is not expected to have clinical sig nificance because it has been identified in 2.7% (59/2178) of chromosomes from a broad population from the 1000 Genomes project (http://www.ncbi.nlm.nih.gov/var iation/tools/1000genomes; rs34616847). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.79

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.46

.;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.0

PhyloP100

1.4

PrimateAI

Uncertain

0.52

Sift4G

Benign

0.37

.;T

Vest4

0.057

ClinPred

0.054

GERP RS

3.7

Varity_R

0.11

gMVP

0.21

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