2-162033665-T-C

Variant names:

• chr2-162033665-T-C
• rs1558957
• NM_001935.4:c.775-12A>G

Variant summary

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

The NM_001935.4(DPP4):​c.775-12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 1,579,598 control chromosomes in the GnomAD database, including 322,104 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 0.72 (40320 hom., cov: 26)
  • Exomes 𝑓: 0.62 (281784 hom.)
• Consequence: DPP4 NM_001935.4 intron
• Scores: Splicing: ADA: 0.0001087
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 18 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=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 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.775-12A>G		intron	N/A	NP_001926.2
	DPP4	NM_001379604.1		c.772-12A>G		intron	N/A	NP_001366533.1	A0A7I2V2X8
	DPP4	NM_001379605.1		c.769-12A>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.775-12A>G		intron	N/A	ENSP00000353731.3	P27487
	DPP4	ENST00000434918.6	TSL:1	n.*263-12A>G		intron	N/A	ENSP00000402259.2	F8WE17
	DPP4	ENST00000461836.6	TSL:1	n.1307-12A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.718 AC: 107711 AN: 150042 Hom.: 40274 Cov.: 26

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.610

Gnomad OTH AF: 0.695

GnomAD2 exomes AF: 0.669 AC: 152719 AN: 228140 AF XY: 0.662

Gnomad AFR exome AF: 0.932

Gnomad AMR exome AF: 0.553

Gnomad ASJ exome AF: 0.731

Gnomad EAS exome AF: 0.994

Gnomad FIN exome AF: 0.689

Gnomad NFE exome AF: 0.608

Gnomad OTH exome AF: 0.635

GnomAD4 exome AF: 0.621 AC: 887225 AN: 1429450 Hom.: 281784 Cov.: 24 AF XY: 0.621 AC XY: 442080 AN XY: 711448

African (AFR) AF: 0.935 AC: 29729 AN: 31800

American (AMR) AF: 0.554 AC: 22006 AN: 39710

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 18401 AN: 25264

East Asian (EAS) AF: 0.991 AC: 38759 AN: 39100

South Asian (SAS) AF: 0.648 AC: 52740 AN: 81364

European-Finnish (FIN) AF: 0.680 AC: 35717 AN: 52526

Middle Eastern (MID) AF: 0.671 AC: 3761 AN: 5602

European-Non Finnish (NFE) AF: 0.591 AC: 647761 AN: 1095142

Other (OTH) AF: 0.651 AC: 38351 AN: 58942

GnomAD4 genome AF: 0.718 AC: 107799 AN: 150148 Hom.: 40320 Cov.: 26 AF XY: 0.720 AC XY: 52679 AN XY: 73164

African (AFR) AF: 0.921 AC: 37789 AN: 41050

American (AMR) AF: 0.596 AC: 9005 AN: 15104

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2540 AN: 3456

East Asian (EAS) AF: 0.990 AC: 5053 AN: 5106

South Asian (SAS) AF: 0.682 AC: 3231 AN: 4736

European-Finnish (FIN) AF: 0.688 AC: 6825 AN: 9926

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.610 AC: 41138 AN: 67488

Other (OTH) AF: 0.697 AC: 1458 AN: 2092

Alfa AF: 0.642 Hom.: 15361

Bravo AF: 0.720

Asia WGS AF: 0.850 AC: 2949 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.76
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.048
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: rs1558957; hg19: chr2-162890175;