Genetic Variant DCP2:p.Pro9Ser (chr5-112976958-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152624.6(DCP2):c.25C>T(p.Pro9Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000683 in 1,596,348 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 1 hom. )

Consequence

DCP2
NM_152624.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.43

Publications

2 publications found

Variant links:

Genes affected

DCP2 (HGNC:24452): (decapping mRNA 2) The protein encoded by this gene is a key component of an mRNA-decapping complex required for degradation of mRNAs, both in normal mRNA turnover, and in nonsense-mediated mRNA decay (NMD). It removes the 7-methyl guanine cap structure from mRNA, prior to its degradation from the 5' end. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Jun 2011]

DCP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18903223).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152624.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCP2	NM_152624.6	MANE Select	c.25C>T	p.Pro9Ser	missense	Exon 1 of 11	NP_689837.2
DCP2	NM_001242377.2		c.25C>T	p.Pro9Ser	missense	Exon 1 of 10	NP_001229306.1	Q8IU60-2
DCP2	NR_038352.2		n.161C>T		non_coding_transcript_exon	Exon 1 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCP2	ENST00000389063.3	TSL:1 MANE Select	c.25C>T	p.Pro9Ser	missense	Exon 1 of 11	ENSP00000373715.2	Q8IU60-1
DCP2	ENST00000515408.5	TSL:1	c.25C>T	p.Pro9Ser	missense	Exon 1 of 10	ENSP00000425770.1	Q8IU60-2
DCP2	ENST00000504961.1	TSL:1	n.146C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000486

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0000654

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:

0.000867

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000338

AC:

AN:

245786

AF XY:

0.000323

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.0000597

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000686

Gnomad OTH exome

AF:

0.000504

GnomAD4 exome

AF:

0.000704

AC:

1016

AN:

1444178

Hom.:

Cov.:

AF XY:

0.000654

AC XY:

468

AN XY:

715776

show subpopulations

African (AFR)

AF:

0.0000909

AC:

AN:

33014

American (AMR)

AF:

0.000114

AC:

AN:

43792

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25848

East Asian (EAS)

AF:

0.00

AC:

AN:

38772

South Asian (SAS)

AF:

0.00

AC:

AN:

85130

European-Finnish (FIN)

AF:

0.000301

AC:

AN:

53178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.000890

AC:

978

AN:

1099290

Other (OTH)

AF:

0.000236

AC:

AN:

59436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

111

166

222

277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

114

152

190

<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:

0.000486

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41450

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000867

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000794

Hom.:

Bravo

AF:

0.000495

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000404

AC:

EpiCase

AF:

0.000552

EpiControl

AF:

0.000480

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

Pathogenic

0.66

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.44

Eigen

Benign

-0.053

Eigen_PC

Benign

0.12

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.017

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

6.4

PrimateAI

Uncertain

0.78

PROVEAN

Pathogenic

-4.9

REVEL

Benign

0.24

Sift

Benign

0.097

Sift4G

Benign

0.16

Polyphen

0.0070

Vest4

0.70

MVP

0.49

MPC

0.30

ClinPred

0.077

GERP RS

4.5

PromoterAI

0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.53

gMVP

0.67

Mutation Taster

=199/101

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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