19-4714032-T-C

Variant names:

• chr19-4714032-T-C
• rs2277733
• NM_139159.5:c.313+49A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139159.5(DPP9):​c.313+49A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,548,806 control chromosomes in the GnomAD database, including 73,314 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 0.40 (15029 hom., cov: 32)
  • Exomes 𝑓: 0.27 (58285 hom.)
• Consequence: DPP9 NM_139159.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• hatipoglu immunodeficiency syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP9	NM_139159.5	c.313+49A>G		intron_variant	Intron 4 of 21	ENST00000262960.14	NP_631898.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP9	ENST00000262960.14	c.313+49A>G		intron_variant	Intron 4 of 21	1	NM_139159.5	ENSP00000262960.8

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60227 AN: 151912 Hom.: 14983 Cov.: 32

Gnomad AFR AF: 0.698

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.382

GnomAD2 exomes AF: 0.334 AC: 60724 AN: 181618 AF XY: 0.326

Gnomad AFR exome AF: 0.712

Gnomad AMR exome AF: 0.461

Gnomad ASJ exome AF: 0.321

Gnomad EAS exome AF: 0.309

Gnomad FIN exome AF: 0.238

Gnomad NFE exome AF: 0.245

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.275 AC: 383668 AN: 1396776 Hom.: 58285 Cov.: 34 AF XY: 0.276 AC XY: 190027 AN XY: 688182

African (AFR) AF: 0.724 AC: 23111 AN: 31910

American (AMR) AF: 0.453 AC: 16400 AN: 36242

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 7182 AN: 22448

East Asian (EAS) AF: 0.330 AC: 12636 AN: 38338

South Asian (SAS) AF: 0.391 AC: 29853 AN: 76440

European-Finnish (FIN) AF: 0.240 AC: 11852 AN: 49364

Middle Eastern (MID) AF: 0.439 AC: 2198 AN: 5004

European-Non Finnish (NFE) AF: 0.243 AC: 262375 AN: 1079504

Other (OTH) AF: 0.314 AC: 18061 AN: 57526

GnomAD4 genome AF: 0.397 AC: 60336 AN: 152030 Hom.: 15029 Cov.: 32 AF XY: 0.396 AC XY: 29444 AN XY: 74326

African (AFR) AF: 0.698 AC: 28927 AN: 41444

American (AMR) AF: 0.421 AC: 6423 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3472

East Asian (EAS) AF: 0.319 AC: 1646 AN: 5160

South Asian (SAS) AF: 0.379 AC: 1827 AN: 4820

European-Finnish (FIN) AF: 0.246 AC: 2607 AN: 10590

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16657 AN: 67974

Other (OTH) AF: 0.381 AC: 802 AN: 2106

Alfa AF: 0.303 Hom.: 12290

Bravo AF: 0.420

Asia WGS AF: 0.402 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.55
DANN	Benign	0.74
PhyloP100		-1.4
PromoterAI		0.036	Neutral
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
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: rs2277733; hg19: chr19-4714044; COSMIC: COSV53594632; COSMIC: COSV53594632;