Genetic Variant ENST00000453163.6:c.*16A>G (chr6-170583012-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 ENST00000453163.6(PDCD2):c.*16A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,586,490 control chromosomes in the GnomAD database, including 211,051 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 0.54 ( 22858 hom., cov: 33)

Exomes 𝑓: 0.51 ( 188193 hom. )

Consequence

PDCD2
ENST00000453163.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.609

Publications

15 publications found

Variant links:

Genes affected

PDCD2 (HGNC:8762): (programmed cell death 2) This gene encodes a nuclear protein expressed in a variety of tissues. Expression of this gene has been shown to be repressed by B-cell CLL/lymphoma 6 (BCL6), a transcriptional repressor required for lymph node germinal center development, suggesting that BCL6 regulates apoptosis by its effects on this protein. Alternative splicing results in multiple transcript variants and pseudogenes have been identified on chromosomes 9 and 12. [provided by RefSeq, Dec 2010]

PDCD2 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 (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD2	NM_002598.4 link	c.658+45A>G		intron_variant	Intron 3 of 5	ENST00000541970.6	NP_002589.2	Q16342-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD2	ENST00000541970.6 link	c.658+45A>G		intron_variant	Intron 3 of 5	1	NM_002598.4	ENSP00000439467.1		Q16342-1

Frequencies

GnomAD3 genomes

AF:

0.543

AC:

82546

AN:

152008

Hom.:

22821

Cov.:

show subpopulations

Gnomad AFR

AF:

0.625

Gnomad AMI

AF:

0.673

Gnomad AMR

AF:

0.471

Gnomad ASJ

AF:

0.498

Gnomad EAS

AF:

0.788

Gnomad SAS

AF:

0.484

Gnomad FIN

AF:

0.486

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.541

GnomAD2 exomes

AF:

0.524

AC:

120561

AN:

230020

AF XY:

0.522

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.452

Gnomad ASJ exome

AF:

0.527

Gnomad EAS exome

AF:

0.790

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.507

Gnomad OTH exome

AF:

0.519

GnomAD4 exome

AF:

0.509

AC:

729881

AN:

1434364

Hom.:

188193

Cov.:

AF XY:

0.508

AC XY:

362449

AN XY:

713010

show subpopulations

African (AFR)

AF:

0.629

AC:

20176

AN:

32058

American (AMR)

AF:

0.458

AC:

17992

AN:

39294

Ashkenazi Jewish (ASJ)

AF:

0.520

AC:

12808

AN:

24654

East Asian (EAS)

AF:

0.792

AC:

31245

AN:

39446

South Asian (SAS)

AF:

0.471

AC:

38483

AN:

81742

European-Finnish (FIN)

AF:

0.480

AC:

24616

AN:

51302

Middle Eastern (MID)

AF:

0.478

AC:

2173

AN:

4546

European-Non Finnish (NFE)

AF:

0.500

AC:

551543

AN:

1102196

Other (OTH)

AF:

0.522

AC:

30845

AN:

59126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

16712

33424

50135

66847

83559

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16214

32428

48642

64856

81070

<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:

0.543

AC:

82632

AN:

152126

Hom.:

22858

Cov.:

AF XY:

0.541

AC XY:

40228

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.626

AC:

25964

AN:

41492

American (AMR)

AF:

0.471

AC:

7198

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.498

AC:

1726

AN:

3464

East Asian (EAS)

AF:

0.788

AC:

4079

AN:

5178

South Asian (SAS)

AF:

0.482

AC:

2326

AN:

4822

European-Finnish (FIN)

AF:

0.486

AC:

5140

AN:

10578

Middle Eastern (MID)

AF:

0.507

AC:

149

AN:

294

European-Non Finnish (NFE)

AF:

0.504

AC:

34291

AN:

67982

Other (OTH)

AF:

0.543

AC:

1147

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1953

3906

5859

7812

9765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.541

Hom.:

9313

Bravo

AF:

0.553

Asia WGS

AF:

0.628

AC:

2184

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

4.9

(source)

DANN

Benign

0.72

PhyloP100

-0.61

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over