rs4849404

chr2-115526559-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP10	NM_020868.6	c.441+587T>C		intron_variant		ENST00000410059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP10	ENST00000410059.6	c.441+587T>C		intron_variant		1	NM_020868.6	A1

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

Gnomad4 AFR AF: 0.0813

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.214

Alfa AF: 0.209 Hom.: 685

Bravo AF: 0.193

Asia WGS AF: 0.337 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	12
Dann	Benign	0.68

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: rs4849404; hg19: chr2-116284135;