chr10-101023921-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.367+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,614,028 control chromosomes in the GnomAD database, including 287,387 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 31608 hom., cov: 33)

Exomes 𝑓: 0.59 ( 255779 hom. )

Consequence

PDZD7
NM_001195263.2 splice_region, intron

Scores

Splicing: ADA: 0.00002722

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.591

Publications

13 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=-0.92).

BP6

Variant 10-101023921-T-C is Benign according to our data. Variant chr10-101023921-T-C is described in ClinVar as Benign. ClinVar VariationId is 46211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZD7	NM_001195263.2 link	c.367+7A>G		splice_region_variant, intron_variant	Intron 3 of 16	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.367+7A>G		splice_region_variant, intron_variant	Intron 3 of 16	5	NM_001195263.2	ENSP00000480489.1		Q9H5P4-3

Frequencies

GnomAD3 genomes

AF:

0.635

AC:

96500

AN:

152082

Hom.:

31573

Cov.:

show subpopulations

Gnomad AFR

AF:

0.796

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.570

Gnomad ASJ

AF:

0.549

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.505

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.602

Gnomad OTH

AF:

0.613

GnomAD2 exomes

AF:

0.565

AC:

142062

AN:

251388

AF XY:

0.564

show subpopulations

Gnomad AFR exome

AF:

0.800

Gnomad AMR exome

AF:

0.477

Gnomad ASJ exome

AF:

0.558

Gnomad EAS exome

AF:

0.402

Gnomad FIN exome

AF:

0.517

Gnomad NFE exome

AF:

0.604

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.589

AC:

860722

AN:

1461828

Hom.:

255779

Cov.:

AF XY:

0.587

AC XY:

426665

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.804

AC:

26931

AN:

33480

American (AMR)

AF:

0.491

AC:

21963

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

14626

AN:

26136

East Asian (EAS)

AF:

0.417

AC:

16538

AN:

39700

South Asian (SAS)

AF:

0.528

AC:

45556

AN:

86258

European-Finnish (FIN)

AF:

0.521

AC:

27801

AN:

53390

Middle Eastern (MID)

AF:

0.663

AC:

3822

AN:

5768

European-Non Finnish (NFE)

AF:

0.601

AC:

667755

AN:

1111976

Other (OTH)

AF:

0.592

AC:

35730

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

22187

44374

66562

88749

110936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18098

36196

54294

72392

90490

<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:

0.635

AC:

96575

AN:

152200

Hom.:

31608

Cov.:

AF XY:

0.626

AC XY:

46552

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.796

AC:

33062

AN:

41546

American (AMR)

AF:

0.569

AC:

8697

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.549

AC:

1903

AN:

3468

East Asian (EAS)

AF:

0.404

AC:

2093

AN:

5178

South Asian (SAS)

AF:

0.522

AC:

2515

AN:

4820

European-Finnish (FIN)

AF:

0.505

AC:

5348

AN:

10590

Middle Eastern (MID)

AF:

0.728

AC:

214

AN:

294

European-Non Finnish (NFE)

AF:

0.601

AC:

40893

AN:

67986

Other (OTH)

AF:

0.610

AC:

1289

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1764

3528

5292

7056

8820

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.611

Hom.:

26952

Bravo

AF:

0.648

Asia WGS

AF:

0.486

AC:

1693

AN:

3478

EpiCase

AF:

0.610

EpiControl

AF:

0.612

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 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. -

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

367+7A>G in Intron 03 of PDZD7: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce and has been identified in 40.2% (2823/7020) of European American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs6584410). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Usher syndrome type 2C

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hearing loss, autosomal recessive 57

Benign:1

Sep 05, 2021

Genome-Nilou Lab

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

0.089

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.29

(source)

DANN

Benign

0.39

PhyloP100

-0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.0

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