2-161994637-T-C

Variant names:

• chr2-161994637-T-C
• rs12617656
• NM_001935.4:c.2199+324A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001935.4(DPP4):​c.2199+324A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,958 control chromosomes in the GnomAD database, including 9,658 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 0.35 (9658 hom., cov: 32)
• Consequence: DPP4 NM_001935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88
• Publications: 25 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 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.2199+324A>G		intron	N/A	NP_001926.2
	DPP4	NM_001379604.1		c.2196+324A>G		intron	N/A	NP_001366533.1	A0A7I2V2X8
	DPP4	NM_001379605.1		c.2193+324A>G		intron	N/A	NP_001366534.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP4	ENST00000360534.8	TSL:1 MANE Select	c.2199+324A>G		intron	N/A	ENSP00000353731.3	P27487
	DPP4	ENST00000434918.6	TSL:1	n.*1918+324A>G		intron	N/A	ENSP00000402259.2	F8WE17
	DPP4	ENST00000676768.1		c.*318A>G		3_prime_UTR	Exon 25 of 25	ENSP00000503008.1	A0A7I2V2R5

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53214 AN: 151838 Hom.: 9658 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.330

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.350 AC: 53235 AN: 151958 Hom.: 9658 Cov.: 32 AF XY: 0.353 AC XY: 26227 AN XY: 74266

African (AFR) AF: 0.343 AC: 14228 AN: 41440

American (AMR) AF: 0.337 AC: 5150 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1428 AN: 3466

East Asian (EAS) AF: 0.650 AC: 3350 AN: 5152

South Asian (SAS) AF: 0.252 AC: 1215 AN: 4816

European-Finnish (FIN) AF: 0.434 AC: 4572 AN: 10544

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.326 AC: 22158 AN: 67956

Other (OTH) AF: 0.328 AC: 692 AN: 2108

Alfa AF: 0.351 Hom.: 15216

Bravo AF: 0.349

Asia WGS AF: 0.411 AC: 1428 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.84
PhyloP100		1.9
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs12617656; hg19: chr2-162851147;