chr2-161994637-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP4	NM_001935.4	c.2199+324A>G		intron_variant	Intron 25 of 25	ENST00000360534.8	NP_001926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP4	ENST00000360534.8	c.2199+324A>G		intron_variant	Intron 25 of 25	1	NM_001935.4	ENSP00000353731.3

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

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.252

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.328

Alfa AF: 0.341 Hom.: 1530

Bravo AF: 0.349

Asia WGS AF: 0.411 AC: 1428 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Benign	0.84

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: rs12617656; hg19: chr2-162851147;