chr2-162059903-G-T

Variant names:

• chr2-162059903-G-T
• rs10490422
• NM_001935.4:c.95-12402C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001935.4(DPP4):​c.95-12402C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0415 in 152,248 control chromosomes in the GnomAD database, including 427 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 0.042 (427 hom., cov: 33)
• Consequence: DPP4 NM_001935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP4	NM_001935.4	c.95-12402C>A		intron_variant	Intron 2 of 25	ENST00000360534.8	NP_001926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP4	ENST00000360534.8	c.95-12402C>A		intron_variant	Intron 2 of 25	1	NM_001935.4	ENSP00000353731.3

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6317 AN: 152130 Hom.: 425 Cov.: 33

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0372

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

GnomAD4 genome AF: 0.0415 AC: 6319 AN: 152248 Hom.: 427 Cov.: 33 AF XY: 0.0487 AC XY: 3624 AN XY: 74434

African (AFR) AF: 0.0261 AC: 1085 AN: 41556

American (AMR) AF: 0.0150 AC: 229 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3472

East Asian (EAS) AF: 0.256 AC: 1325 AN: 5178

South Asian (SAS) AF: 0.245 AC: 1181 AN: 4822

European-Finnish (FIN) AF: 0.0755 AC: 799 AN: 10578

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0203 AC: 1378 AN: 68016

Other (OTH) AF: 0.0430 AC: 91 AN: 2116

Alfa AF: 0.0257 Hom.: 227

Bravo AF: 0.0330

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.41
PhyloP100		-0.25
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: rs10490422; hg19: chr2-162916413;