Genetic Variant PDZD2:c.1254+106T>C (chr5-32000377-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.1254+106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 1,219,698 control chromosomes in the GnomAD database, including 423,177 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 0.70 ( 41010 hom., cov: 34)

Exomes 𝑓: 0.84 ( 382167 hom. )

Consequence

PDZD2
NM_178140.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0780

Publications

19 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=-0.91).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 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.1254+106T>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.1254+106T>C	intron	N/A	ENSP00000402033.1	O15018-1
PDZD2	ENST00000942338.1		c.979-9953T>C	intron	N/A	ENSP00000612397.1
PDZD2	ENST00000502489.5	TSL:2	n.1010+106T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.700

AC:

106445

AN:

152094

Hom.:

41013

Cov.:

show subpopulations

Gnomad AFR

AF:

0.384

Gnomad AMI

AF:

0.907

Gnomad AMR

AF:

0.704

Gnomad ASJ

AF:

0.813

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.775

Gnomad FIN

AF:

0.846

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.881

Gnomad OTH

AF:

0.708

GnomAD4 exome

AF:

0.836

AC:

892560

AN:

1067488

Hom.:

382167

AF XY:

0.837

AC XY:

454384

AN XY:

542858

show subpopulations

African (AFR)

AF:

0.378

AC:

9773

AN:

25858

American (AMR)

AF:

0.718

AC:

30163

AN:

42004

Ashkenazi Jewish (ASJ)

AF:

0.818

AC:

17290

AN:

21134

East Asian (EAS)

AF:

0.362

AC:

13652

AN:

37686

South Asian (SAS)

AF:

0.788

AC:

55815

AN:

70864

European-Finnish (FIN)

AF:

0.849

AC:

43953

AN:

51740

Middle Eastern (MID)

AF:

0.752

AC:

3694

AN:

4910

European-Non Finnish (NFE)

AF:

0.888

AC:

680643

AN:

766130

Other (OTH)

AF:

0.797

AC:

37577

AN:

47162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

6474

12948

19421

25895

32369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12590

25180

37770

50360

62950

<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:

0.699

AC:

106458

AN:

152210

Hom.:

41010

Cov.:

AF XY:

0.697

AC XY:

51848

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.384

AC:

15920

AN:

41486

American (AMR)

AF:

0.703

AC:

10764

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.813

AC:

2823

AN:

3472

East Asian (EAS)

AF:

0.339

AC:

1751

AN:

5162

South Asian (SAS)

AF:

0.777

AC:

3749

AN:

4828

European-Finnish (FIN)

AF:

0.846

AC:

8979

AN:

10614

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.881

AC:

59929

AN:

68026

Other (OTH)

AF:

0.706

AC:

1492

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

1316

2632

3949

5265

6581

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

800

1600

2400

3200

4000

<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:

0.811

Hom.:

174501

Bravo

AF:

0.673

Asia WGS

AF:

0.543

AC:

1894

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.5

(source)

DANN

Benign

0.65

PhyloP100

-0.078

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