Genetic Variant DCP2:p.Arg274Cys (chr5-113003955-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152624.6(DCP2):c.820C>T(p.Arg274Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

DCP2
NM_152624.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.27

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3309492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCP2	NM_152624.6 link	c.820C>T	p.Arg274Cys	missense_variant	Exon 8 of 11	ENST00000389063.3	NP_689837.2	Q8IU60-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCP2	ENST00000389063.3 link	c.820C>T	p.Arg274Cys	missense_variant	Exon 8 of 11	1	NM_152624.6	ENSP00000373715.2		Q8IU60-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251296

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461780

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000624

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.820C>T (p.R274C) alteration is located in exon 8 (coding exon 8) of the DCP2 gene. This alteration results from a C to T substitution at nucleotide position 820, causing the arginine (R) at amino acid position 274 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;T

Eigen

Benign

-0.071

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.0075

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.3

N;N

REVEL

Benign

0.20

Sift

Benign

0.059

T;T

Sift4G

Uncertain

0.010

D;T

Polyphen

0.0030

B;B

Vest4

0.60

MutPred

0.38

Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);

MVP

0.73

MPC

0.35

ClinPred

0.70

GERP RS

4.8

Varity_R

0.22

gMVP

0.48

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