rs4849404

Variant names:

• chr2-115526559-T-C
• rs4849404
• NM_020868.6:c.441+587T>C

Variant summary

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

The NM_020868.6(DPP10):​c.441+587T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,116 control chromosomes in the GnomAD database, including 3,347 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 0.19 (3347 hom., cov: 32)
• Consequence: DPP10 NM_020868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 6 publications found

Genes affected

DPP10 (HGNC:20823): (dipeptidyl peptidase like 10) This gene encodes a single-pass type II membrane protein that is a member of the S9B family in clan SC of the serine proteases. This protein has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties. Mutations in this gene have been associated with asthma. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020868.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP10	NM_020868.6	MANE Select	c.441+587T>C		intron	N/A	NP_065919.3
	DPP10	NM_001321905.3		c.492+587T>C		intron	N/A	NP_001308834.2
	DPP10	NM_001178034.1		c.453+587T>C		intron	N/A	NP_001171505.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP10	ENST00000410059.6	TSL:1 MANE Select	c.441+587T>C		intron	N/A	ENSP00000386565.1
	DPP10	ENST00000393147.6	TSL:1	c.453+587T>C		intron	N/A	ENSP00000376855.2
	DPP10	ENST00000310323.12	TSL:1	c.420+587T>C		intron	N/A	ENSP00000309066.8

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28461 AN: 151998 Hom.: 3333 Cov.: 32

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.211

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.187 AC: 28494 AN: 152116 Hom.: 3347 Cov.: 32 AF XY: 0.196 AC XY: 14541 AN XY: 74340

African (AFR) AF: 0.0813 AC: 3377 AN: 41550

American (AMR) AF: 0.331 AC: 5050 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3470

East Asian (EAS) AF: 0.390 AC: 2006 AN: 5146

South Asian (SAS) AF: 0.271 AC: 1306 AN: 4826

European-Finnish (FIN) AF: 0.243 AC: 2573 AN: 10570

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12985 AN: 67996

Other (OTH) AF: 0.214 AC: 452 AN: 2112

Alfa AF: 0.205 Hom.: 686

Bravo AF: 0.193

Asia WGS AF: 0.337 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		0.42
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: rs4849404; hg19: chr2-116284135;