2-114451828-A-G

Variant names:

• chr2-114451828-A-G
• rs1430092
• NM_020868.6:c.60+8990A>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.60+8990A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 152,094 control chromosomes in the GnomAD database, including 63,456 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 0.91 (63456 hom., cov: 31)
• Consequence: DPP10 NM_020868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 2 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP10	NM_020868.6	c.60+8990A>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.60+8990A>G		intron_variant	Intron 1 of 25	1	NM_020868.6	ENSP00000386565.1
DPP10	ENST00000436732.5	c.-163+8990A>G		intron_variant	Intron 1 of 4	4		ENSP00000391092.1

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138863 AN: 151976 Hom.: 63425 Cov.: 31

Gnomad AFR AF: 0.919

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.917

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

GnomAD4 genome AF: 0.914 AC: 138950 AN: 152094 Hom.: 63456 Cov.: 31 AF XY: 0.914 AC XY: 67963 AN XY: 74352

African (AFR) AF: 0.918 AC: 38132 AN: 41518

American (AMR) AF: 0.911 AC: 13905 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2913 AN: 3468

East Asian (EAS) AF: 0.905 AC: 4651 AN: 5142

South Asian (SAS) AF: 0.902 AC: 4348 AN: 4818

European-Finnish (FIN) AF: 0.919 AC: 9749 AN: 10604

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62149 AN: 67958

Other (OTH) AF: 0.915 AC: 1931 AN: 2110

Alfa AF: 0.910 Hom.: 92494

Bravo AF: 0.913

Asia WGS AF: 0.881 AC: 3067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.8
DANN	Benign	0.70
PhyloP100		0.18
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: rs1430092; hg19: chr2-115209405;