2-114636950-C-T

Variant names:

• chr2-114636950-C-T
• rs12996109
• NM_020868.6:c.60+194112C>T

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+194112C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 151,762 control chromosomes in the GnomAD database, including 2,319 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 0.16 (2319 hom., cov: 32)
• Consequence: DPP10 NM_020868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP10	NM_020868.6	c.60+194112C>T		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+194112C>T		intron_variant	Intron 1 of 25	1	NM_020868.6	ENSP00000386565.1
DPP10	ENST00000409163.5	c.-91+173524C>T		intron_variant	Intron 2 of 26	2		ENSP00000387038.1
DPP10	ENST00000436732.5	c.-163+194112C>T		intron_variant	Intron 1 of 4	4		ENSP00000391092.1
DPP10	ENST00000461250.5	n.597-70167C>T		intron_variant	Intron 2 of 7	2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23958 AN: 151642 Hom.: 2318 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.158 AC: 23998 AN: 151762 Hom.: 2319 Cov.: 32 AF XY: 0.156 AC XY: 11602 AN XY: 74194

African (AFR) AF: 0.245 AC: 10070 AN: 41144

American (AMR) AF: 0.136 AC: 2078 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3466

East Asian (EAS) AF: 0.136 AC: 705 AN: 5166

South Asian (SAS) AF: 0.131 AC: 631 AN: 4822

European-Finnish (FIN) AF: 0.0925 AC: 980 AN: 10600

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8711 AN: 67972

Other (OTH) AF: 0.153 AC: 324 AN: 2114

Alfa AF: 0.137 Hom.: 2156

Bravo AF: 0.164

Asia WGS AF: 0.135 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	8.6
DANN	Benign	0.62
PhyloP100		0.55
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: rs12996109; hg19: chr2-115394527;