Genetic Variant PDZD2:c.-360-93T>C (chr5-31798796-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178140.4(PDZD2):c.-360-93T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 167,430 control chromosomes in the GnomAD database, including 2,388 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2310 hom., cov: 32)

Exomes 𝑓: 0.086 ( 78 hom. )

Consequence

PDZD2
NM_178140.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

4 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178140.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZD2	NM_178140.4	MANE Select	c.-360-93T>C		intron	N/A	NP_835260.2	O15018-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDZD2	ENST00000438447.2	TSL:1 MANE Select	c.-360-93T>C	intron	N/A	ENSP00000402033.1	O15018-1
PDZD2	ENST00000502824.1	TSL:1	n.89-93T>C	intron	N/A
PDZD2	ENST00000942338.1		c.-360-93T>C	intron	N/A	ENSP00000612397.1

Frequencies

GnomAD3 genomes

AF:

0.152

AC:

23179

AN:

152044

Hom.:

2306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.0930

Gnomad ASJ

AF:

0.0827

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.0712

Gnomad FIN

AF:

0.0597

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.120

Gnomad OTH

AF:

0.136

GnomAD4 exome

AF:

0.0856

AC:

1307

AN:

15268

Hom.:

AF XY:

0.0859

AC XY:

677

AN XY:

7878

show subpopulations

African (AFR)

AF:

0.258

AC:

AN:

376

American (AMR)

AF:

0.0565

AC:

146

AN:

2584

Ashkenazi Jewish (ASJ)

AF:

0.0708

AC:

AN:

240

East Asian (EAS)

AF:

0.00475

AC:

AN:

1052

South Asian (SAS)

AF:

0.0679

AC:

AN:

1252

European-Finnish (FIN)

AF:

0.0417

AC:

AN:

312

Middle Eastern (MID)

AF:

0.100

AC:

AN:

European-Non Finnish (NFE)

AF:

0.100

AC:

873

AN:

8702

Other (OTH)

AF:

0.0944

AC:

AN:

720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

114

171

228

285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.152

AC:

23196

AN:

152162

Hom.:

2310

Cov.:

AF XY:

0.145

AC XY:

10783

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.285

AC:

11799

AN:

41460

American (AMR)

AF:

0.0928

AC:

1420

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0827

AC:

287

AN:

3470

East Asian (EAS)

AF:

0.0110

AC:

AN:

5174

South Asian (SAS)

AF:

0.0706

AC:

341

AN:

4828

European-Finnish (FIN)

AF:

0.0597

AC:

634

AN:

10614

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.120

AC:

8150

AN:

67998

Other (OTH)

AF:

0.136

AC:

288

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

948

1896

2843

3791

4739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<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:

0.124

Hom.:

2282

Bravo

AF:

0.161

Asia WGS

AF:

0.0680

AC:

236

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.039

(source)

DANN

Benign

0.55

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over