chr19-4679870-G-A

Position:

• chr19-4679870-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_139159.5(DPP9):​c.2551C>T​(p.Gln851Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPP9 NM_139159.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.07

Genes affected

DPP9 (HGNC:18648): (dipeptidyl peptidase 9) This gene encodes a protein that is a member of the S9B family in clan SC of the serine proteases. The protein has been shown to have post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. Although the activity of this protein is similar to that of dipeptidyl peptidase 4 (DPP4), it does not appear to be membrane bound. In general, dipeptidyl peptidases appear to be involved in the regulation of the activity of their substrates and have been linked to a variety of diseases including type 2 diabetes, obesity and cancer. Several transcript variants of this gene have been described but not fully characterized. [provided by RefSeq, Jul 2008]

DPP9-AS1 (HGNC:50706): (DPP9 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 19-4679870-G-A is Pathogenic according to our data. Variant chr19-4679870-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2500000.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP9	NM_139159.5	c.2551C>T	p.Gln851Ter	stop_gained	21/22	ENST00000262960.14
DPP9-AS1	NR_164163.1	n.258+331G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP9	ENST00000262960.14	c.2551C>T	p.Gln851Ter	stop_gained	21/22	1	NM_139159.5	P1
DPP9-AS1	ENST00000381796.1	n.258+331G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hatipoglu immunodeficiency syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	43
DANN	Uncertain	1.0
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
MutationTaster	Benign	1.0	D;D
Vest4		0.74
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-4679882;