rs41268649

chr2-162008623-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001935.4(DPP4):c.1926G>A(p.Ser642=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DPP4	NM_001935.4	c.1926G>A	p.Ser642=	synonymous_variant	22/26	ENST00000360534.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP4	ENST00000360534.8	c.1926G>A	p.Ser642=	synonymous_variant	22/26	1	NM_001935.4	P3

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4533 AN: 151976 Hom.: 104 Cov.: 32

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

GnomAD3 exomes AF: 0.0279 AC: 7019 AN: 251274 Hom.: 151 AF XY: 0.0277 AC XY: 3768 AN XY: 135808

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 SAS exome AF: 0.00931

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.: 31 AF XY: 0.0434 AC XY: 31586 AN XY: 727018

Gnomad4 AFR exome AF: 0.00774

Gnomad4 AMR exome AF: 0.0212

Gnomad4 ASJ exome AF: 0.0132

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0108

Gnomad4 FIN exome AF: 0.0289

Gnomad4 NFE exome AF: 0.0529

Gnomad4 OTH exome AF: 0.0411

GnomAD4 genome AF: 0.0298 AC: 4532 AN: 152094 Hom.: 104 Cov.: 32 AF XY: 0.0273 AC XY: 2031 AN XY: 74324

Gnomad4 AFR AF: 0.00846

Gnomad4 AMR AF: 0.0279

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.00686

Gnomad4 FIN AF: 0.0258

Gnomad4 NFE AF: 0.0487

Gnomad4 OTH AF: 0.0304

Alfa AF: 0.0365 Hom.: 48

Bravo AF: 0.0292

Asia WGS AF: 0.00433 AC: 15 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
Dann	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

LitVar

Other links and lift over

dbSNP: rs41268649; hg19: chr2-162865133; COSMIC: COSV62109948;