Variant chr10-101010570-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001195263.2(PDZD7):c.2319T>C(p.Arg773=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,515,998 control chromosomes in the GnomAD database, including 518,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. RSRSR773R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.82 ( 50356 hom., cov: 30)

Exomes 𝑓: 0.83 ( 468101 hom. )

Consequence

PDZD7
NM_001195263.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.522

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 10-101010570-A-G is Benign according to our data. Variant chr10-101010570-A-G is described in ClinVar as [Benign]. Clinvar id is 44124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101010570-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.522 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD7	NM_001195263.2 linkuse as main transcript	c.2319T>C	p.Arg773=	synonymous_variant	15/17	ENST00000619208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD7	ENST00000619208.6 linkuse as main transcript	c.2319T>C	p.Arg773=	synonymous_variant	15/17	5	NM_001195263.2	P1	Q9H5P4-3
PDZD7	ENST00000474125.7 linkuse as main transcript	c.*2266T>C		3_prime_UTR_variant, NMD_transcript_variant	11/13	2

Frequencies

GnomAD3 genomes

AF:

0.815

AC:

123470

AN:

151424

Hom.:

50309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.788

Gnomad AMI

AF:

0.854

Gnomad AMR

AF:

0.823

Gnomad ASJ

AF:

0.821

Gnomad EAS

AF:

0.675

Gnomad SAS

AF:

0.781

Gnomad FIN

AF:

0.843

Gnomad MID

AF:

0.771

Gnomad NFE

AF:

0.839

Gnomad OTH

AF:

0.808

GnomAD3 exomes

AF:

0.808

AC:

102589

AN:

127004

Hom.:

41568

AF XY:

0.807

AC XY:

55472

AN XY:

68772

show subpopulations

Gnomad AFR exome

AF:

0.787

Gnomad AMR exome

AF:

0.820

Gnomad ASJ exome

AF:

0.825

Gnomad EAS exome

AF:

0.684

Gnomad SAS exome

AF:

0.776

Gnomad FIN exome

AF:

0.846

Gnomad NFE exome

AF:

0.838

Gnomad OTH exome

AF:

0.810

GnomAD4 exome

AF:

0.829

AC:

1131112

AN:

1364456

Hom.:

468101

Cov.:

AF XY:

0.827

AC XY:

555077

AN XY:

670886

show subpopulations

Gnomad4 AFR exome

AF:

0.793

Gnomad4 AMR exome

AF:

0.821

Gnomad4 ASJ exome

AF:

0.829

Gnomad4 EAS exome

AF:

0.655

Gnomad4 SAS exome

AF:

0.779

Gnomad4 FIN exome

AF:

0.842

Gnomad4 NFE exome

AF:

0.841

Gnomad4 OTH exome

AF:

0.810

GnomAD4 genome

AF:

0.815

AC:

123570

AN:

151542

Hom.:

50356

Cov.:

AF XY:

0.813

AC XY:

60233

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.788

Gnomad4 AMR

AF:

0.823

Gnomad4 ASJ

AF:

0.821

Gnomad4 EAS

AF:

0.675

Gnomad4 SAS

AF:

0.782

Gnomad4 FIN

AF:

0.843

Gnomad4 NFE

AF:

0.839

Gnomad4 OTH

AF:

0.807

Alfa

AF:

0.835

Hom.:

16983

Bravo

AF:

0.814

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Arg773Arg in Exon 15 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 26.3% (31/118) of chr omosomes from a population in the dbSNP database (http://www.ncbi.nlm.nih.gov/pr ojects/SNP; rs807022). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 02, 2014	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 02, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Usher syndrome type 2C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Hearing loss, autosomal recessive 57

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

4.4

DANN

Benign

0.60

Splicing

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