rs2109069

Positions:

• chr19-4719431-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139159.5(DPP9):​c.56+420C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 168,646 control chromosomes in the GnomAD database, including 6,524 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 0.27 (5874 hom., cov: 33)
  • Exomes 𝑓: 0.26 (650 hom.)
• Consequence: DPP9 NM_139159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP9	NM_139159.5	c.56+420C>T		intron_variant		ENST00000262960.14	NP_631898.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP9	ENST00000262960.14	c.56+420C>T		intron_variant		1	NM_139159.5	ENSP00000262960.8

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41204 AN: 151884 Hom.: 5865 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.263 AC: 4373 AN: 16646 Hom.: 650 Cov.: 0 AF XY: 0.264 AC XY: 2339 AN XY: 8866

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.279

GnomAD4 genome AF: 0.271 AC: 41238 AN: 152000 Hom.: 5874 Cov.: 33 AF XY: 0.269 AC XY: 20008 AN XY: 74290

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.267

Alfa AF: 0.299 Hom.: 13020

Bravo AF: 0.266

Asia WGS AF: 0.153 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.45
DANN	Benign	0.22

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

LitVar

Other links and lift over

dbSNP: rs2109069; hg19: chr19-4719443;