2-114890006-T-G

Variant names:

• chr2-114890006-T-G
• rs998429
• NM_020868.6:c.61-419233T>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.61-419233T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,168 control chromosomes in the GnomAD database, including 3,688 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 0.20 (3688 hom., cov: 32)
• Consequence: DPP10 NM_020868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 4 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 (AMR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP10	NM_020868.6	c.61-419233T>G		intron_variant	Intron 1 of 25	ENST00000410059.6	NP_065919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP10	ENST00000410059.6	c.61-419233T>G		intron_variant	Intron 1 of 25	1	NM_020868.6	ENSP00000386565.1
DPP10	ENST00000409163.5	c.-90-419233T>G		intron_variant	Intron 2 of 26	2		ENSP00000387038.1
DPP10	ENST00000436732.5	c.-162-160142T>G		intron_variant	Intron 1 of 4	4		ENSP00000391092.1
DPP10	ENST00000461250.5	n.654+182832T>G		intron_variant	Intron 3 of 7	2

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31032 AN: 152050 Hom.: 3687 Cov.: 32

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.204 AC: 31029 AN: 152168 Hom.: 3688 Cov.: 32 AF XY: 0.203 AC XY: 15137 AN XY: 74388

African (AFR) AF: 0.0765 AC: 3177 AN: 41550

American (AMR) AF: 0.278 AC: 4242 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3466

East Asian (EAS) AF: 0.104 AC: 538 AN: 5174

South Asian (SAS) AF: 0.265 AC: 1277 AN: 4824

European-Finnish (FIN) AF: 0.233 AC: 2467 AN: 10588

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17425 AN: 67974

Other (OTH) AF: 0.269 AC: 565 AN: 2104

Alfa AF: 0.238 Hom.: 13849

Bravo AF: 0.199

Asia WGS AF: 0.174 AC: 606 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	5.5
DANN	Benign	0.61
PhyloP100		0.0010
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs998429; hg19: chr2-115647583;