rs41268649

Variant names:

• chr2-162008623-C-T
• rs41268649
• NM_001935.4:c.1926G>A
• DPP4 p.Ser642Ser

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 7 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001935.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP4	NM_001935.4	MANE Select	c.1926G>A	p.Ser642Ser	synonymous	Exon 22 of 26	NP_001926.2
	DPP4	NM_001379604.1		c.1923G>A	p.Ser641Ser	synonymous	Exon 22 of 26	NP_001366533.1	A0A7I2V2X8
	DPP4	NM_001379605.1		c.1920G>A	p.Ser640Ser	synonymous	Exon 22 of 26	NP_001366534.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP4	ENST00000360534.8	TSL:1 MANE Select	c.1926G>A	p.Ser642Ser	synonymous	Exon 22 of 26	ENSP00000353731.3	P27487
	DPP4	ENST00000434918.6	TSL:1	n.*1645G>A		non_coding_transcript_exon	Exon 23 of 27	ENSP00000402259.2	F8WE17
	DPP4	ENST00000434918.6	TSL:1	n.*1645G>A		3_prime_UTR	Exon 23 of 27	ENSP00000402259.2	F8WE17

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

GnomAD2 exomes AF: 0.0279 AC: 7019 AN: 251274 AF XY: 0.0277

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

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: 4 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: 27 AN: 5768

European-Non Finnish (NFE) AF: 0.0529 AC: 58786 AN: 1111606

Other (OTH) AF: 0.0411 AC: 2479 AN: 60370

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

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: 49 AN: 3472

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.00686 AC: 33 AN: 4812

European-Finnish (FIN) AF: 0.0258 AC: 273 AN: 10578

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0487 AC: 3311 AN: 67986

Other (OTH) AF: 0.0304 AC: 64 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	6.8
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)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41268649;

hg19: chr2-162865133;

COSMIC: COSV62109948;