10-101010521-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001195263.2(PDZD7):c.2368A>G(p.Lys790Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0385 in 1,530,350 control chromosomes in the GnomAD database, including 2,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.072 ( 756 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1333 hom. )

Consequence

PDZD7
NM_001195263.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.91

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=0.0016091168).

BP6

Variant 10-101010521-T-C is Benign according to our data. Variant chr10-101010521-T-C is described in ClinVar as [Benign]. Clinvar id is 44127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2 link	c.2368A>G	p.Lys790Glu	missense_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.2368A>G	p.Lys790Glu	missense_variant	Exon 15 of 17	5	NM_001195263.2	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000474125.7 link	n.*2315A>G		non_coding_transcript_exon_variant	Exon 11 of 13	2		ENSP00000474447.1	S4R3J9
PDZD7	ENST00000474125.7 link	n.*2315A>G		3_prime_UTR_variant	Exon 11 of 13	2		ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes

AF:

0.0721

AC:

10842

AN:

150352

Hom.:

752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.0135

Gnomad AMR

AF:

0.0355

Gnomad ASJ

AF:

0.0576

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0391

Gnomad FIN

AF:

0.0477

Gnomad MID

AF:

0.0382

Gnomad NFE

AF:

0.0273

Gnomad OTH

AF:

0.0649

GnomAD2 exomes

AF:

0.0389

AC:

5187

AN:

133472

AF XY:

0.0387

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.0254

Gnomad ASJ exome

AF:

0.0532

Gnomad EAS exome

AF:

0.000476

Gnomad FIN exome

AF:

0.0507

Gnomad NFE exome

AF:

0.0288

Gnomad OTH exome

AF:

0.0335

GnomAD4 exome

AF:

0.0348

AC:

48008

AN:

1379880

Hom.:

1333

Cov.:

AF XY:

0.0347

AC XY:

23570

AN XY:

680000

show subpopulations

African (AFR)

AF:

0.186

AC:

5852

AN:

31502

American (AMR)

AF:

0.0267

AC:

951

AN:

35578

Ashkenazi Jewish (ASJ)

AF:

0.0513

AC:

1287

AN:

25104

East Asian (EAS)

AF:

0.000141

AC:

AN:

35580

South Asian (SAS)

AF:

0.0444

AC:

3517

AN:

79134

European-Finnish (FIN)

AF:

0.0468

AC:

1584

AN:

33822

Middle Eastern (MID)

AF:

0.0426

AC:

242

AN:

5678

European-Non Finnish (NFE)

AF:

0.0300

AC:

32231

AN:

1075800

Other (OTH)

AF:

0.0405

AC:

2339

AN:

57682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

3079

6159

9238

12318

15397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0722

AC:

10866

AN:

150470

Hom.:

756

Cov.:

AF XY:

0.0706

AC XY:

5179

AN XY:

73392

show subpopulations

African (AFR)

AF:

0.181

AC:

7466

AN:

41322

American (AMR)

AF:

0.0353

AC:

527

AN:

14912

Ashkenazi Jewish (ASJ)

AF:

0.0576

AC:

199

AN:

3452

East Asian (EAS)

AF:

0.000580

AC:

AN:

5176

South Asian (SAS)

AF:

0.0389

AC:

184

AN:

4730

European-Finnish (FIN)

AF:

0.0477

AC:

491

AN:

10286

Middle Eastern (MID)

AF:

0.0445

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0273

AC:

1838

AN:

67344

Other (OTH)

AF:

0.0643

AC:

133

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

474

948

1422

1896

2370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0313

Hom.:

145

Bravo

AF:

0.0757

TwinsUK

AF:

0.0324

AC:

120

ALSPAC

AF:

0.0278

AC:

107

ExAC

AF:

0.0319

AC:

718

Asia WGS

AF:

0.0260

AC:

AN:

3476

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

not specified

Benign:2

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Lys790Glu in Exon 15 of PDZD7: This variant is not expected to have clinical sig nificance because it has been identified in 13.6% (16/118) of chromosomes from a population in the dbSNP database (http://www.ncbi.nlm.nih.gov/projects/SNP; rs1 11287837). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

(source)

DANN

Benign

0.60

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.51

.;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

PhyloP100

3.9

PrimateAI

Uncertain

0.65

Sift4G

Benign

0.55

.;T

Vest4

0.13

ClinPred

0.11

GERP RS

5.5

Varity_R

0.20

gMVP

0.23

Splicing

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

Publications

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10-101010521-T-C

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