2-162014451-T-A

Variant names:

• chr2-162014451-T-A
• rs200348396
• NM_001935.4:c.1582A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001935.4(DPP4):​c.1582A>T​(p.Met528Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M528V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPP4 NM_001935.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.91
• Publications: 2 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28249985).

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.1582A>T	p.Met528Leu	missense	Exon 19 of 26	NP_001926.2
	DPP4	NM_001379604.1		c.1579A>T	p.Met527Leu	missense	Exon 19 of 26	NP_001366533.1	A0A7I2V2X8
	DPP4	NM_001379605.1		c.1576A>T	p.Met526Leu	missense	Exon 19 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.1582A>T	p.Met528Leu	missense	Exon 19 of 26	ENSP00000353731.3	P27487
	DPP4	ENST00000434918.6	TSL:1	n.*1301A>T		non_coding_transcript_exon	Exon 20 of 27	ENSP00000402259.2	F8WE17
	DPP4	ENST00000434918.6	TSL:1	n.*1301A>T		3_prime_UTR	Exon 20 of 27	ENSP00000402259.2	F8WE17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	0.0023
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.068
Sift	Benign	0.17	T
Sift4G	Benign	0.77	T
Polyphen		0.058	B
Vest4		0.51
MutPred		0.41		Gain of ubiquitination at K523 (P = 0.1084)
MVP		0.29
MPC		0.14
ClinPred		0.64	D
GERP RS		5.8
Varity_R		0.61
gMVP		0.69
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs200348396; hg19: chr2-162870961;