5-31983322-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_178140.4(PDZD2):c.644G>A(p.Arg215Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,614,184 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

PDZD2
NM_178140.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 8.63

Variant links:

Genes affected

PDZD2 (HGNC:18486): (PDZ domain containing 2) The protein encoded by this gene contains six PDZ domains and shares sequence similarity with pro-interleukin-16 (pro-IL-16). Like pro-IL-16, the encoded protein localizes to the endoplasmic reticulum and is thought to be cleaved by a caspase to produce a secreted peptide containing two PDZ domains. In addition, this gene is upregulated in primary prostate tumors and may be involved in the early stages of prostate tumorigenesis. [provided by RefSeq, Dec 2015]

PDZD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, PDZD2

BP4

Computational evidence support a benign effect (MetaRNN=0.008613676).

BP6

Variant 5-31983322-G-A is Benign according to our data. Variant chr5-31983322-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3034906.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 239 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD2	NM_178140.4 linkuse as main transcript	c.644G>A	p.Arg215Gln	missense_variant	3/25	ENST00000438447.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD2	ENST00000438447.2 linkuse as main transcript	c.644G>A	p.Arg215Gln	missense_variant	3/25	1	NM_178140.4	P1	O15018-1
PDZD2	ENST00000502489.5 linkuse as main transcript	n.400G>A		non_coding_transcript_exon_variant	2/18	2
PDZD2	ENST00000513852.1 linkuse as main transcript	n.363G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00157

AC:

239

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00550

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000497

AC:

125

AN:

251352

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00707

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000180

AC:

263

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

112

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00651

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.00157

AC:

239

AN:

152294

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00548

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000313

Hom.:

Bravo

AF:

0.00198

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000610

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

PDZD2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 08, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.33

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.34

Sift

Uncertain

0.018

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.49

MVP

0.83

MPC

1.1

ClinPred

0.070

GERP RS

5.2

Varity_R

0.27

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

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