Genetic Variant PDZD7:c.367+7A>G (chr10-101023921-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 46211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101023921-T-C is described in Lovd as [Benign].

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

GnomAD3 exomes

AF:

0.565

AC:

142062

AN:

251388

Hom.:

41234

AF XY:

0.564

AC XY:

76625

AN XY:

135878

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 SAS exome

AF:

0.524

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

Gnomad4 AFR exome

AF:

0.804

Gnomad4 AMR exome

AF:

0.491

Gnomad4 ASJ exome

AF:

0.560

Gnomad4 EAS exome

AF:

0.417

Gnomad4 SAS exome

AF:

0.528

Gnomad4 FIN exome

AF:

0.521

Gnomad4 NFE exome

AF:

0.601

Gnomad4 OTH exome

AF:

0.592

GnomAD4 genome

AF:

0.635

AC:

96575

AN:

152200

Hom.:

31608

Cov.:

AF XY:

0.626

AC XY:

46552

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.796

Gnomad4 AMR

AF:

0.569

Gnomad4 ASJ

AF:

0.549

Gnomad4 EAS

AF:

0.404

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.505

Gnomad4 NFE

AF:

0.601

Gnomad4 OTH

AF:

0.610

Alfa

AF:

0.611

Hom.:

19868

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

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.29

DANN

Benign

0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over