Genetic Variant PDCD2:p.Gln247Arg (chr6-170580024-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002598.4(PDCD2):c.740A>G(p.Gln247Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PDCD2
NM_002598.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06032911).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002598.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDCD2	NM_002598.4	MANE Select	c.740A>G	p.Gln247Arg	missense	Exon 4 of 6	NP_002589.2
PDCD2	NM_001199462.2		c.641A>G	p.Gln214Arg	missense	Exon 5 of 7	NP_001186391.1	Q16342-3
PDCD2	NM_001363655.2		c.740A>G	p.Gln247Arg	missense	Exon 4 of 6	NP_001350584.1	F5H4V9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PDCD2	ENST00000541970.6	TSL:1 MANE Select	c.740A>G	p.Gln247Arg	missense	Exon 4 of 6	ENSP00000439467.1	Q16342-1
PDCD2	ENST00000392090.6	TSL:1	c.641A>G	p.Gln214Arg	missense	Exon 5 of 7	ENSP00000375940.2	Q16342-3
PDCD2	ENST00000542896.5	TSL:2	c.740A>G	p.Gln247Arg	missense	Exon 4 of 6	ENSP00000439914.1	F5H4V9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1448076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721482

African (AFR)

AF:

0.00

AC:

AN:

33200

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39616

South Asian (SAS)

AF:

0.00

AC:

AN:

85962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53312

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099548

Other (OTH)

AF:

0.00

AC:

AN:

59946

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.083

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.68

M_CAP

Benign

0.0011

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.92

PhyloP100

1.3

PrimateAI

Benign

0.32

PROVEAN

Benign

0.89

REVEL

Benign

0.065

Sift

Benign

1.0

Sift4G

Benign

0.69

Polyphen

0.0

Vest4

0.094

MutPred

0.53

Gain of MoRF binding (P = 0.0095)

MVP

0.081

MPC

0.085

ClinPred

0.030

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.061

gMVP

0.28

Mutation Taster

=97/3

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over