2-115343901-G-C

Variant names:

• chr2-115343901-G-C
• rs138406948
• NM_020868.6:c.260G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020868.6(DPP10):​c.260G>C​(p.Arg87Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,874 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R87Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DPP10 NM_020868.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.260G>C	p.Arg87Pro	missense	Exon 3 of 26	NP_065919.3
	DPP10	NM_001321905.3		c.311G>C	p.Arg104Pro	missense	Exon 4 of 27	NP_001308834.2
	DPP10	NM_001178034.1		c.272G>C	p.Arg91Pro	missense	Exon 3 of 26	NP_001171505.1	Q8N608

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP10	ENST00000410059.6	TSL:1 MANE Select	c.260G>C	p.Arg87Pro	missense	Exon 3 of 26	ENSP00000386565.1	Q8N608-1
	DPP10	ENST00000393147.6	TSL:1	c.272G>C	p.Arg91Pro	missense	Exon 3 of 26	ENSP00000376855.2	Q8N608-3
	DPP10	ENST00000310323.12	TSL:1	c.239G>C	p.Arg80Pro	missense	Exon 3 of 26	ENSP00000309066.8	Q8N608-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457874 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725282

African (AFR) AF: 0.00 AC: 0 AN: 33330

American (AMR) AF: 0.00 AC: 0 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.00 AC: 0 AN: 85630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109756

Other (OTH) AF: 0.00 AC: 0 AN: 60200

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.00024
Eigen_PC	Benign	0.014
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.5
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.25
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.013	D
Polyphen		0.55	P
Vest4		0.75
MutPred		0.54		Gain of catalytic residue at W88 (P = 0.0118)
MVP		0.78
MPC		0.45
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.75
gMVP		0.92
Mutation Taster		=74/26	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: rs138406948; hg19: chr2-116101477;