Variant 6-170584376-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002598.4(PDCD2):c.206C>G(p.Pro69Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,490,742 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 97 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 78 hom. )

Consequence

PDCD2
NM_002598.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031739473).

BP6

Variant 6-170584376-G-C is Benign according to our data. Variant chr6-170584376-G-C is described in ClinVar as [Benign]. Clinvar id is 784105.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD2	NM_002598.4 linkuse as main transcript	c.206C>G	p.Pro69Arg	missense_variant	1/6	ENST00000541970.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD2	ENST00000541970.6 linkuse as main transcript	c.206C>G	p.Pro69Arg	missense_variant	1/6	1	NM_002598.4	P1	Q16342-1

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2879

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0662

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00414

AC:

602

AN:

145504

Hom.:

AF XY:

0.00317

AC XY:

265

AN XY:

83696

show subpopulations

Gnomad AFR exome

AF:

0.0670

Gnomad AMR exome

AF:

0.00351

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000151

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.00252

GnomAD4 exome

AF:

0.00181

AC:

2419

AN:

1338456

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

1114

AN XY:

664752

show subpopulations

Gnomad4 AFR exome

AF:

0.0688

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000833

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000117

Gnomad4 OTH exome

AF:

0.00454

GnomAD4 genome

AF:

0.0189

AC:

2876

AN:

152286

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

1295

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0660

Gnomad4 AMR

AF:

0.00536

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.0144

Hom.:

Bravo

AF:

0.0218

ESP6500AA

AF:

0.0398

AC:

144

ESP6500EA

AF:

0.000133

AC:

ExAC

AF:

0.00494

AC:

575

Asia WGS

AF:

0.00347

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 02, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;.;.;.;T;.

Eigen

Benign

0.041

Eigen_PC

Benign

0.010

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.74

T;T;T;T;T;T;T

MetaRNN

Benign

0.0032

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.8

M;.;.;M;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.6

N;N;N;N;N;.;N

REVEL

Benign

0.13

Sift

Benign

0.068

T;T;T;T;T;.;T

Sift4G

Benign

0.41

T;T;T;T;T;T;T

Polyphen

0.19

B;.;P;.;.;.;.

Vest4

0.24

MVP

0.45

MPC

0.086

ClinPred

0.057

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.13

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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