chr2-162011827-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001935.4(DPP4):​c.1798A>G​(p.Thr600Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

DPP4
NM_001935.4 missense

Scores

5
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02
Variant links:
Genes affected
DPP4 (HGNC:3009): (dipeptidyl peptidase 4) The DPP4 gene encodes dipeptidyl peptidase 4, which is identical to adenosine deaminase complexing protein-2, and to the T-cell activation antigen CD26. It is an intrinsic type II transmembrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides. Dipeptidyl peptidase 4 is highly involved in glucose and insulin metabolism, as well as in immune regulation. This protein was shown to be a functional receptor for Middle East respiratory syndrome coronavirus (MERS-CoV), and protein modeling suggests that it may play a similar role with SARS-CoV-2, the virus responsible for COVID-19. [provided by RefSeq, Apr 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DPP4NM_001935.4 linkuse as main transcriptc.1798A>G p.Thr600Ala missense_variant 20/26 ENST00000360534.8 NP_001926.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DPP4ENST00000360534.8 linkuse as main transcriptc.1798A>G p.Thr600Ala missense_variant 20/261 NM_001935.4 ENSP00000353731 P3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
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
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 26, 2023The c.1798A>G (p.T600A) alteration is located in exon 20 (coding exon 20) of the DPP4 gene. This alteration results from a A to G substitution at nucleotide position 1798, causing the threonine (T) at amino acid position 600 to be replaced by an alanine (A). 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
0.22
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.026
D
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.6
D
REVEL
Benign
0.25
Sift
Uncertain
0.015
D
Sift4G
Uncertain
0.018
D
Polyphen
0.96
D
Vest4
0.65
MutPred
0.42
Gain of catalytic residue at T600 (P = 0.2439);
MVP
0.66
MPC
0.61
ClinPred
0.98
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.55
gMVP
0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-162868337; API