rs540213991

Variant names:

• chr9-137049932-C-G
• rs540213991
• NM_203468.3:c.1087G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-137049932-C-G
• chr9-137049932-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203468.3(ENTPD2):​c.1087G>C​(p.Val363Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 33)
• Consequence: ENTPD2 NM_203468.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17458525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3	c.1087G>C	p.Val363Leu	missense_variant	Exon 7 of 9	ENST00000355097.7	NP_982293.1
ENTPD2	NM_001246.4	c.1087G>C	p.Val363Leu	missense_variant	Exon 7 of 9		NP_001237.1
ENTPD2	XM_011519212.3	c.778G>C	p.Val260Leu	missense_variant	Exon 6 of 8		XP_011517514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD2	ENST00000355097.7	c.1087G>C	p.Val363Leu	missense_variant	Exon 7 of 9	1	NM_203468.3	ENSP00000347213.2
ENTPD2	ENST00000312665.7	c.1087G>C	p.Val363Leu	missense_variant	Exon 7 of 9	1		ENSP00000312494.5

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152178 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74344

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.72
DEOGEN2	Benign	0.018	T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.9	M;M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.48	N;N
REVEL	Benign	0.10
Sift	Benign	0.43	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.60	P;P
Vest4		0.37
MutPred		0.49		Gain of glycosylation at P362 (P = 0.0943);Gain of glycosylation at P362 (P = 0.0943);
MVP		0.39
MPC		0.056
ClinPred		0.52	D
GERP RS		2.4
Varity_R		0.056
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs540213991; hg19: chr9-139944384;