2-162073469-A-G

Variant names:

• chr2-162073469-A-G
• rs17574
• NM_001935.4:c.24T>C

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.24T>C​(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,613,416 control chromosomes in the GnomAD database, including 89,960 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 0.28 (6556 hom., cov: 32)
  • Exomes 𝑓: 0.33 (83404 hom.)
• Consequence: DPP4 NM_001935.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 29 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]

DPP4-DT (HGNC:40191): (DPP4 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=0.179 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 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.24T>C	p.Leu8Leu	synonymous	Exon 2 of 26	NP_001926.2
	DPP4	NM_001379604.1		c.24T>C	p.Leu8Leu	synonymous	Exon 2 of 26	NP_001366533.1	A0A7I2V2X8
	DPP4	NM_001379605.1		c.24T>C	p.Leu8Leu	synonymous	Exon 2 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.24T>C	p.Leu8Leu	synonymous	Exon 2 of 26	ENSP00000353731.3	P27487
	DPP4	ENST00000434918.6	TSL:1	n.24T>C		non_coding_transcript_exon	Exon 2 of 27	ENSP00000402259.2	F8WE17
	DPP4	ENST00000461836.6	TSL:1	n.505T>C		non_coding_transcript_exon	Exon 1 of 10

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42947 AN: 152012 Hom.: 6553 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.301

GnomAD2 exomes AF: 0.275 AC: 69042 AN: 251408 AF XY: 0.284

Gnomad AFR exome AF: 0.238

Gnomad AMR exome AF: 0.179

Gnomad ASJ exome AF: 0.315

Gnomad EAS exome AF: 0.0365

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.339

Gnomad OTH exome AF: 0.300

GnomAD4 exome AF: 0.330 AC: 482471 AN: 1461288 Hom.: 83404 Cov.: 39 AF XY: 0.330 AC XY: 239891 AN XY: 726982

African (AFR) AF: 0.240 AC: 8023 AN: 33460

American (AMR) AF: 0.183 AC: 8181 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 8172 AN: 26130

East Asian (EAS) AF: 0.0400 AC: 1589 AN: 39698

South Asian (SAS) AF: 0.313 AC: 26991 AN: 86224

European-Finnish (FIN) AF: 0.240 AC: 12793 AN: 53408

Middle Eastern (MID) AF: 0.344 AC: 1931 AN: 5616

European-Non Finnish (NFE) AF: 0.356 AC: 395220 AN: 1111678

Other (OTH) AF: 0.324 AC: 19571 AN: 60354

GnomAD4 genome AF: 0.282 AC: 42967 AN: 152128 Hom.: 6556 Cov.: 32 AF XY: 0.274 AC XY: 20372 AN XY: 74374

African (AFR) AF: 0.242 AC: 10036 AN: 41500

American (AMR) AF: 0.236 AC: 3609 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1092 AN: 3466

East Asian (EAS) AF: 0.0445 AC: 230 AN: 5170

South Asian (SAS) AF: 0.299 AC: 1442 AN: 4824

European-Finnish (FIN) AF: 0.231 AC: 2442 AN: 10590

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23145 AN: 67972

Other (OTH) AF: 0.298 AC: 631 AN: 2116

Alfa AF: 0.316 Hom.: 15825

Bravo AF: 0.279

Asia WGS AF: 0.190 AC: 662 AN: 3478

EpiCase AF: 0.343

EpiControl AF: 0.345

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	17
DANN	Benign	0.81
PhyloP100		0.18
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
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: rs17574; hg19: chr2-162929979; COSMIC: COSV62106574; COSMIC: COSV62106574;