chr2-114985970-A-G

Variant names:

• chr2-114985970-A-G
• rs949577
• NM_020868.6:c.61-323269A>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.61-323269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,182 control chromosomes in the GnomAD database, including 3,595 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 0.21 (3595 hom., cov: 33)
• Consequence: DPP10 NM_020868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP10	NM_020868.6	c.61-323269A>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.61-323269A>G		intron_variant	Intron 1 of 25	1	NM_020868.6	ENSP00000386565.1
DPP10	ENST00000409163.5	c.-90-323269A>G		intron_variant	Intron 2 of 26	2		ENSP00000387038.1
DPP10	ENST00000436732.5	c.-162-64178A>G		intron_variant	Intron 1 of 4	4		ENSP00000391092.1
DPP10	ENST00000461250.5	n.654+278796A>G		intron_variant	Intron 3 of 7	2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31737 AN: 152062 Hom.: 3590 Cov.: 33

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.368

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.243

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

GnomAD4 genome AF: 0.209 AC: 31753 AN: 152182 Hom.: 3595 Cov.: 33 AF XY: 0.216 AC XY: 16084 AN XY: 74390

African (AFR) AF: 0.120 AC: 4994 AN: 41556

American (AMR) AF: 0.249 AC: 3807 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 899 AN: 3462

East Asian (EAS) AF: 0.283 AC: 1465 AN: 5172

South Asian (SAS) AF: 0.374 AC: 1805 AN: 4826

European-Finnish (FIN) AF: 0.297 AC: 3148 AN: 10584

Middle Eastern (MID) AF: 0.355 AC: 103 AN: 290

European-Non Finnish (NFE) AF: 0.217 AC: 14737 AN: 67996

Other (OTH) AF: 0.245 AC: 516 AN: 2110

Alfa AF: 0.227 Hom.: 2538

Bravo AF: 0.197

Asia WGS AF: 0.337 AC: 1171 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.74
DANN	Benign	0.35
PhyloP100		-0.62
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: rs949577; hg19: chr2-115743547;