Genetic Variant DPP4:c.775-12A>G (chr2-162033665-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001935.4(DPP4):c.775-12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 1,579,598 control chromosomes in the GnomAD database, including 322,104 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 40320 hom., cov: 26)

Exomes 𝑓: 0.62 ( 281784 hom. )

Consequence

DPP4
NM_001935.4 intron

Scores

Splicing: ADA: 0.0001087

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

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]

DPP4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP4	NM_001935.4 link	c.775-12A>G		intron_variant	Intron 9 of 25	ENST00000360534.8	NP_001926.2	P27487

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP4	ENST00000360534.8 link	c.775-12A>G		intron_variant	Intron 9 of 25	1	NM_001935.4	ENSP00000353731.3		P27487

Frequencies

GnomAD3 genomes

AF:

0.718

AC:

107711

AN:

150042

Hom.:

40274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.920

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.597

Gnomad ASJ

AF:

0.735

Gnomad EAS

AF:

0.990

Gnomad SAS

AF:

0.683

Gnomad FIN

AF:

0.688

Gnomad MID

AF:

0.701

Gnomad NFE

AF:

0.610

Gnomad OTH

AF:

0.695

GnomAD3 exomes

AF:

0.669

AC:

152719

AN:

228140

Hom.:

53100

AF XY:

0.662

AC XY:

81711

AN XY:

123408

show subpopulations

Gnomad AFR exome

AF:

0.932

Gnomad AMR exome

AF:

0.553

Gnomad ASJ exome

AF:

0.731

Gnomad EAS exome

AF:

0.994

Gnomad SAS exome

AF:

0.655

Gnomad FIN exome

AF:

0.689

Gnomad NFE exome

AF:

0.608

Gnomad OTH exome

AF:

0.635

GnomAD4 exome

AF:

0.621

AC:

887225

AN:

1429450

Hom.:

281784

Cov.:

AF XY:

0.621

AC XY:

442080

AN XY:

711448

show subpopulations

Gnomad4 AFR exome

AF:

0.935

Gnomad4 AMR exome

AF:

0.554

Gnomad4 ASJ exome

AF:

0.728

Gnomad4 EAS exome

AF:

0.991

Gnomad4 SAS exome

AF:

0.648

Gnomad4 FIN exome

AF:

0.680

Gnomad4 NFE exome

AF:

0.591

Gnomad4 OTH exome

AF:

0.651

GnomAD4 genome

AF:

0.718

AC:

107799

AN:

150148

Hom.:

40320

Cov.:

AF XY:

0.720

AC XY:

52679

AN XY:

73164

show subpopulations

Gnomad4 AFR

AF:

0.921

Gnomad4 AMR

AF:

0.596

Gnomad4 ASJ

AF:

0.735

Gnomad4 EAS

AF:

0.990

Gnomad4 SAS

AF:

0.682

Gnomad4 FIN

AF:

0.688

Gnomad4 NFE

AF:

0.610

Gnomad4 OTH

AF:

0.697

Alfa

AF:

0.648

Hom.:

9073

Bravo

AF:

0.720

Asia WGS

AF:

0.850

AC:

2949

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.048

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over