5-113001569-C-T

Variant summary

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

The NM_152624.6(DCP2):​c.701C>T​(p.Pro234Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DCP2
NM_152624.6 missense, splice_region

Scores

2
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79
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]

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=0.3576287).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DCP2NM_152624.6 linkc.701C>T p.Pro234Leu missense_variant, splice_region_variant Exon 7 of 11 ENST00000389063.3 NP_689837.2 Q8IU60-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DCP2ENST00000389063.3 linkc.701C>T p.Pro234Leu missense_variant, splice_region_variant Exon 7 of 11 1 NM_152624.6 ENSP00000373715.2 Q8IU60-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461728
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727174
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.701C>T (p.P234L) alteration is located in exon 7 (coding exon 7) of the DCP2 gene. This alteration results from a C to T substitution at nucleotide position 701, causing the proline (P) at amino acid position 234 to be replaced by a leucine (L). 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
Pathogenic
0.69
BayesDel_addAF
Uncertain
0.042
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.29
.;T
Eigen
Benign
-0.072
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.36
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Benign
0.20
Sift
Benign
0.21
T;D
Sift4G
Benign
0.31
T;T
Polyphen
0.026
B;B
Vest4
0.60
MutPred
0.45
Loss of disorder (P = 0.0289);Loss of disorder (P = 0.0289);
MVP
0.67
MPC
0.34
ClinPred
0.74
D
GERP RS
6.1
Varity_R
0.30
gMVP
0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-112337266; COSMIC: COSV66617241; COSMIC: COSV66617241; API