NM_020868.6:c.109A>G

Variant names:

• chr2-115309287-A-G
• rs149146861
• NM_020868.6:c.109A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020868.6(DPP10):​c.109A>G​(p.Ile37Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: DPP10 NM_020868.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.72
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.415372).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020868.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP10	NM_020868.6	MANE Select	c.109A>G	p.Ile37Val	missense	Exon 2 of 26	NP_065919.3
	DPP10	NM_001178036.3		c.-42A>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 27	NP_001171507.2	Q8N608-4
	DPP10	NM_001321910.3		c.-42A>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 27	NP_001308839.2	Q8N608-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP10	ENST00000410059.6	TSL:1 MANE Select	c.109A>G	p.Ile37Val	missense	Exon 2 of 26	ENSP00000386565.1	Q8N608-1
	DPP10	ENST00000393147.6	TSL:1	c.121A>G	p.Ile41Val	missense	Exon 2 of 26	ENSP00000376855.2	Q8N608-3
	DPP10	ENST00000310323.12	TSL:1	c.88A>G	p.Ile30Val	missense	Exon 2 of 26	ENSP00000309066.8	Q8N608-2

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 151988 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 250962 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461434 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727022

African (AFR) AF: 0.0000598 AC: 2 AN: 33454

American (AMR) AF: 0.0000447 AC: 2 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39660

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111698

Other (OTH) AF: 0.0000331 AC: 2 AN: 60378

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 151988 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74238

African (AFR) AF: 0.00 AC: 0 AN: 41384

American (AMR) AF: 0.0000656 AC: 1 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67966

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000384 Hom.: 0

Bravo AF: 0.0000264

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.047	T
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		8.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.25
Sift	Benign	0.093	T
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.50
MVP		0.58
MPC		0.52
ClinPred		0.69	D
GERP RS		5.6
Varity_R		0.18
gMVP		0.49
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs149146861; hg19: chr2-116066863;