10-101010325-T-G

Position:

chr10-101010325-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001195263.2(PDZD7):c.2564A>C(p.Asn855Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,535,802 control chromosomes in the GnomAD database, including 535,835 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.82 ( 50866 hom., cov: 32)

Exomes 𝑓: 0.84 ( 484969 hom. )

Consequence

PDZD7
NM_001195263.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.131

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 (MetaRNN=8.920337E-7).

BP6

Variant 10-101010325-T-G is Benign according to our data. Variant chr10-101010325-T-G is described in ClinVar as [Benign]. Clinvar id is 44129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-101010325-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD7	NM_001195263.2 linkuse as main transcript	c.2564A>C	p.Asn855Thr	missense_variant	15/17	ENST00000619208.6	NP_001182192.1	Q9H5P4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PDZD7	ENST00000619208.6 linkuse as main transcript	c.2564A>C	p.Asn855Thr	missense_variant	15/17	5	NM_001195263.2	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000474125.7 linkuse as main transcript	n.*2511A>C		non_coding_transcript_exon_variant	11/13	2		ENSP00000474447.1	S4R3J9
PDZD7	ENST00000474125.7 linkuse as main transcript	n.*2511A>C		3_prime_UTR_variant	11/13	2		ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes

AF:

0.817

AC:

124141

AN:

152038

Hom.:

50818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.856

Gnomad AMR

AF:

0.829

Gnomad ASJ

AF:

0.821

Gnomad EAS

AF:

0.675

Gnomad SAS

AF:

0.784

Gnomad FIN

AF:

0.831

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.848

Gnomad OTH

AF:

0.809

GnomAD3 exomes

AF:

0.815

AC:

112381

AN:

137968

Hom.:

46000

AF XY:

0.814

AC XY:

60943

AN XY:

74846

show subpopulations

Gnomad AFR exome

AF:

0.776

Gnomad AMR exome

AF:

0.823

Gnomad ASJ exome

AF:

0.828

Gnomad EAS exome

AF:

0.684

Gnomad SAS exome

AF:

0.781

Gnomad FIN exome

AF:

0.831

Gnomad NFE exome

AF:

0.850

Gnomad OTH exome

AF:

0.817

GnomAD4 exome

AF:

0.836

AC:

1157120

AN:

1383646

Hom.:

484969

Cov.:

AF XY:

0.835

AC XY:

569693

AN XY:

682674

show subpopulations

Gnomad4 AFR exome

AF:

0.781

Gnomad4 AMR exome

AF:

0.823

Gnomad4 ASJ exome

AF:

0.833

Gnomad4 EAS exome

AF:

0.654

Gnomad4 SAS exome

AF:

0.782

Gnomad4 FIN exome

AF:

0.832

Gnomad4 NFE exome

AF:

0.850

Gnomad4 OTH exome

AF:

0.817

GnomAD4 genome

AF:

0.817

AC:

124240

AN:

152156

Hom.:

50866

Cov.:

AF XY:

0.814

AC XY:

60533

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.778

Gnomad4 AMR

AF:

0.829

Gnomad4 ASJ

AF:

0.821

Gnomad4 EAS

AF:

0.675

Gnomad4 SAS

AF:

0.784

Gnomad4 FIN

AF:

0.831

Gnomad4 NFE

AF:

0.848

Gnomad4 OTH

AF:

0.808

Alfa

AF:

0.838

Hom.:

122178

Bravo

AF:

0.817

TwinsUK

AF:

0.857

AC:

3177

ALSPAC

AF:

0.845

AC:

3256

ExAC

AF:

0.862

AC:

35422

Asia WGS

AF:

0.712

AC:

2478

AN:

3478

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	Eurofins Ntd Llc (ga)	Jul 02, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Asn855Thr in Exon 15 of PDZD7: This variant is not expected to have clinical sig nificance because it has been identified in 40.7% (35/86) of chromosomes from a population in the dbSNP database (http://www.ncbi.nlm.nih.gov/projects/SNP; rs80 7023). -
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	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:3

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

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

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

3.4

DANN

Benign

0.68

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.13

.;T

MetaRNN

Benign

8.9e-7

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.30

Sift4G

Benign

0.61

.;T

Vest4

0.0070

ClinPred

0.0088

GERP RS

1.4

Varity_R

0.046

gMVP

0.13

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