rs717522

Positions:

• chr2-115444847-A-G
• chr2-115444847-A-T

Variant summary

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

The NM_020868.6(DPP10):​c.272-54663A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,188 control chromosomes in the GnomAD database, including 3,236 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 0.14 (3236 hom., cov: 32)
• Consequence: DPP10 NM_020868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP10	NM_020868.6	c.272-54663A>G		intron_variant		ENST00000410059.6	NP_065919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP10	ENST00000410059.6	c.272-54663A>G		intron_variant		1	NM_020868.6	ENSP00000386565	A1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21162 AN: 152070 Hom.: 3233 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0792

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0315

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.139 AC: 21191 AN: 152188 Hom.: 3236 Cov.: 32 AF XY: 0.137 AC XY: 10183 AN XY: 74412

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.0789

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0315

Gnomad4 NFE AF: 0.0301

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0182 Hom.: 18

Bravo AF: 0.154

Asia WGS AF: 0.157 AC: 546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.32
DANN	Benign	0.70

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: rs717522; hg19: chr2-116202423;