chr2-114855888-G-A

Variant names:

• chr2-114855888-G-A
• rs4353658
• NM_020868.6:c.60+413050G>A

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+413050G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,282 control chromosomes in the GnomAD database, including 10,496 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 0.36 (10496 hom., cov: 31)
• Consequence: DPP10 NM_020868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP10	NM_020868.6	c.60+413050G>A		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+413050G>A		intron_variant	Intron 1 of 25	1	NM_020868.6	ENSP00000386565.1
DPP10	ENST00000409163.5	c.-91+392462G>A		intron_variant	Intron 2 of 26	2		ENSP00000387038.1
DPP10	ENST00000436732.5	c.-162-194260G>A		intron_variant	Intron 1 of 4	4		ENSP00000391092.1
DPP10	ENST00000461250.5	n.654+148714G>A		intron_variant	Intron 3 of 7	2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54518 AN: 151170 Hom.: 10491 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.361 AC: 54554 AN: 151282 Hom.: 10496 Cov.: 31 AF XY: 0.358 AC XY: 26475 AN XY: 73868

African (AFR) AF: 0.271 AC: 11186 AN: 41266

American (AMR) AF: 0.338 AC: 5138 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3468

East Asian (EAS) AF: 0.126 AC: 649 AN: 5152

South Asian (SAS) AF: 0.513 AC: 2458 AN: 4794

European-Finnish (FIN) AF: 0.326 AC: 3368 AN: 10328

Middle Eastern (MID) AF: 0.432 AC: 126 AN: 292

European-Non Finnish (NFE) AF: 0.430 AC: 29143 AN: 67786

Other (OTH) AF: 0.401 AC: 839 AN: 2090

Alfa AF: 0.403 Hom.: 49247

Bravo AF: 0.351

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.69
PhyloP100		0.78
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: rs4353658; hg19: chr2-115613465;