chr2-162074215-T-A

Variant names:

• chr2-162074215-T-A
• rs13015258
• NM_001935.4:c.-234A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001935.4(DPP4):​c.-234A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,063,698 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: DPP4 NM_001935.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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.-234A>T		5_prime_UTR	Exon 1 of 26	NP_001926.2
	DPP4	NM_001379604.1		c.-234A>T		5_prime_UTR	Exon 1 of 26	NP_001366533.1	A0A7I2V2X8
	DPP4	NM_001379605.1		c.-234A>T		5_prime_UTR	Exon 1 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.-234A>T		5_prime_UTR	Exon 1 of 26	ENSP00000353731.3	P27487
	DPP4	ENST00000676810.1		c.-234A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	ENSP00000503161.1	A0A7I2V2X8
	DPP4	ENST00000676810.1		c.-234A>T		5_prime_UTR	Exon 1 of 26	ENSP00000503161.1	A0A7I2V2X8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000188 AC: 2 AN: 1063698 Hom.: 0 Cov.: 34 AF XY: 0.00000199 AC XY: 1 AN XY: 503166

African (AFR) AF: 0.00 AC: 0 AN: 21830

American (AMR) AF: 0.00 AC: 0 AN: 7692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13120

East Asian (EAS) AF: 0.00 AC: 0 AN: 24860

South Asian (SAS) AF: 0.00 AC: 0 AN: 19866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2768

European-Non Finnish (NFE) AF: 0.00000220 AC: 2 AN: 910396

Other (OTH) AF: 0.00 AC: 0 AN: 42136

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.36
PhyloP100		-2.2
PromoterAI		-0.015	Neutral

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: rs13015258; hg19: chr2-162930725;