chr2-114965457-G-A

Variant names:

• chr2-114965457-G-A
• rs12469474
• NM_020868.6:c.61-343782G>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.61-343782G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,968 control chromosomes in the GnomAD database, including 4,183 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 0.23 (4183 hom., cov: 31)
• Consequence: DPP10 NM_020868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• 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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP10	NM_020868.6	c.61-343782G>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.61-343782G>A		intron_variant	Intron 1 of 25	1	NM_020868.6	ENSP00000386565.1
DPP10	ENST00000409163.5	c.-90-343782G>A		intron_variant	Intron 2 of 26	2		ENSP00000387038.1
DPP10	ENST00000436732.5	c.-162-84691G>A		intron_variant	Intron 1 of 4	4		ENSP00000391092.1
DPP10	ENST00000461250.5	n.654+258283G>A		intron_variant	Intron 3 of 7	2

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34482 AN: 151850 Hom.: 4182 Cov.: 31

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.227 AC: 34493 AN: 151968 Hom.: 4183 Cov.: 31 AF XY: 0.233 AC XY: 17322 AN XY: 74270

African (AFR) AF: 0.132 AC: 5484 AN: 41460

American (AMR) AF: 0.278 AC: 4243 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1400 AN: 5128

South Asian (SAS) AF: 0.368 AC: 1774 AN: 4818

European-Finnish (FIN) AF: 0.299 AC: 3152 AN: 10532

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16480 AN: 67984

Other (OTH) AF: 0.270 AC: 569 AN: 2110

Alfa AF: 0.250 Hom.: 2630

Bravo AF: 0.217

Asia WGS AF: 0.335 AC: 1167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.0
DANN	Benign	0.89
PhyloP100		0.33
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: rs12469474; hg19: chr2-115723034;