rs371094769

Variant names:

• chr9-137049050-C-G
• rs371094769
• NM_203468.3:c.1175G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-137049050-C-G
• chr9-137049050-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_203468.3(ENTPD2):​c.1175G>C​(p.Arg392Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000795 in 1,534,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R392W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: ENTPD2 NM_203468.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.563
• Publications: 1 publications found

Genes affected

ENTPD2 (HGNC:3364): (ectonucleoside triphosphate diphosphohydrolase 2) The protein encoded by this gene is the type 2 enzyme of the ecto-nucleoside triphosphate diphosphohydrolase family (E-NTPDase). E-NTPDases are a family of ecto-nucleosidases that hydrolyze 5'-triphosphates. This ecto-ATPase is an integral membrane protein. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.015553981).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203468.3. 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
	ENTPD2	NM_203468.3	MANE Select	c.1175G>C	p.Arg392Pro	missense	Exon 8 of 9	NP_982293.1	Q9Y5L3-1
	ENTPD2	NM_001246.4		c.1150-44G>C		intron	N/A	NP_001237.1	Q9Y5L3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENTPD2	ENST00000355097.7	TSL:1 MANE Select	c.1175G>C	p.Arg392Pro	missense	Exon 8 of 9	ENSP00000347213.2	Q9Y5L3-1
	ENTPD2	ENST00000312665.7	TSL:1	c.1150-44G>C		intron	N/A	ENSP00000312494.5	Q9Y5L3-2
	ENTPD2	ENST00000460614.1	TSL:1	n.564G>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152210 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000360 AC: 47 AN: 130424 AF XY: 0.000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00380

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000755

GnomAD4 exome AF: 0.0000760 AC: 105 AN: 1381790 Hom.: 0 Cov.: 68 AF XY: 0.0000748 AC XY: 51 AN XY: 681706

African (AFR) AF: 0.00 AC: 0 AN: 31254

American (AMR) AF: 0.00 AC: 0 AN: 35230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25022

East Asian (EAS) AF: 0.00183 AC: 65 AN: 35504

South Asian (SAS) AF: 0.000164 AC: 13 AN: 79110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5578

European-Non Finnish (NFE) AF: 0.00000279 AC: 3 AN: 1076874

Other (OTH) AF: 0.000416 AC: 24 AN: 57644

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152328 Hom.: 0 Cov.: 34 AF XY: 0.000188 AC XY: 14 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41584

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00231 AC: 12 AN: 5186

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000132

ExAC AF: 0.000143 AC: 12

Asia WGS AF: 0.00144 AC: 5 AN: 3476

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	Benign	0.090
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.3
DANN	Benign	0.64
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.41	N
PhyloP100		-0.56
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.12
Sift	Benign	0.050	D
Sift4G	Benign	0.061	T
Polyphen		0.89	P
Vest4		0.18
MutPred		0.64		Loss of MoRF binding (P = 0.0149)
MVP		0.22
MPC		0.076
ClinPred		0.038	T
GERP RS		-5.0
Varity_R		0.26
gMVP		0.80
Mutation Taster		=89/11	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: rs371094769; hg19: chr9-139943502;