rs12997234

Variant names:

• chr2-115609171-A-G
• rs12997234
• NM_020868.6:c.442-80516A>G

Variant summary

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

The NM_020868.6(DPP10):​c.442-80516A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 152,216 control chromosomes in the GnomAD database, including 598 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 0.070 (598 hom., cov: 32)
• Consequence: DPP10 NM_020868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP10	NM_020868.6	c.442-80516A>G		intron_variant	Intron 5 of 25	ENST00000410059.6	NP_065919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP10	ENST00000410059.6	c.442-80516A>G		intron_variant	Intron 5 of 25	1	NM_020868.6	ENSP00000386565.1

Frequencies

GnomAD3 genomes AF: 0.0706 AC: 10733 AN: 152098 Hom.: 598 Cov.: 32

Gnomad AFR AF: 0.0172

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0449

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0373

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.0569

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

GnomAD4 genome AF: 0.0705 AC: 10728 AN: 152216 Hom.: 598 Cov.: 32 AF XY: 0.0727 AC XY: 5409 AN XY: 74418

African (AFR) AF: 0.0172 AC: 713 AN: 41562

American (AMR) AF: 0.0447 AC: 684 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.0369 AC: 178 AN: 4828

European-Finnish (FIN) AF: 0.203 AC: 2149 AN: 10574

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0986 AC: 6704 AN: 67988

Other (OTH) AF: 0.0563 AC: 119 AN: 2114

Alfa AF: 0.0967 Hom.: 113

Bravo AF: 0.0563

Asia WGS AF: 0.0130 AC: 45 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.80
PhyloP100		0.22
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: rs12997234; hg19: chr2-116366747;