dbSNP rs41268649: DPP4:p.Ser642Ser (chr2-162008623-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_001935.4(DPP4):c.1926G>A(p.Ser642Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 1,613,440 control chromosomes in the GnomAD database, including 1,850 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 0.030 ( 104 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1746 hom. )

Consequence

DPP4
NM_001935.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.308

Publications

7 publications found

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 was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP7

Synonymous conserved (PhyloP=-0.308 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP4	NM_001935.4 link	c.1926G>A	p.Ser642Ser	synonymous_variant	Exon 22 of 26	ENST00000360534.8	NP_001926.2	P27487

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP4	ENST00000360534.8 link	c.1926G>A	p.Ser642Ser	synonymous_variant	Exon 22 of 26	1	NM_001935.4	ENSP00000353731.3		P27487

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

4533

AN:

151976

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00849

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0279

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00685

Gnomad FIN

AF:

0.0258

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0487

Gnomad OTH

AF:

0.0307

GnomAD2 exomes

AF:

0.0279

AC:

7019

AN:

251274

AF XY:

0.0277

show subpopulations

Gnomad AFR exome

AF:

0.00843

Gnomad AMR exome

AF:

0.0201

Gnomad ASJ exome

AF:

0.0144

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0275

Gnomad NFE exome

AF:

0.0437

Gnomad OTH exome

AF:

0.0310

GnomAD4 exome

AF:

0.0447

AC:

65322

AN:

1461346

Hom.:

1746

Cov.:

AF XY:

0.0434

AC XY:

31586

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.00774

AC:

259

AN:

33444

American (AMR)

AF:

0.0212

AC:

948

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.0132

AC:

346

AN:

26120

East Asian (EAS)

AF:

0.000101

AC:

AN:

39696

South Asian (SAS)

AF:

0.0108

AC:

928

AN:

86252

European-Finnish (FIN)

AF:

0.0289

AC:

1545

AN:

53410

Middle Eastern (MID)

AF:

0.00468

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0529

AC:

58786

AN:

1111606

Other (OTH)

AF:

0.0411

AC:

2479

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

3258

6515

9773

13030

16288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2208

4416

6624

8832

11040

<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:

0.0298

AC:

4532

AN:

152094

Hom.:

104

Cov.:

AF XY:

0.0273

AC XY:

2031

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00846

AC:

351

AN:

41484

American (AMR)

AF:

0.0279

AC:

426

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3472

East Asian (EAS)

AF:

0.000773

AC:

AN:

5172

South Asian (SAS)

AF:

0.00686

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.0258

AC:

273

AN:

10578

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0487

AC:

3311

AN:

67986

Other (OTH)

AF:

0.0304

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

220

440

660

880

1100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0365

Hom.:

Bravo

AF:

0.0292

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0441

EpiControl

AF:

0.0418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

6.8

(source)

DANN

Benign

0.68

PhyloP100

-0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=88/12

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over