rs1371786503

Variant names:

• chr9-137048961-C-G
• NM_203468.3:c.1264G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-137048961-C-G
• chr9-137048961-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.1264G>C​(p.Gly422Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,796 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G422A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ENTPD2 NM_203468.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504

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=0.121760964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3	c.1264G>C	p.Gly422Arg	missense_variant	Exon 8 of 9	ENST00000355097.7	NP_982293.1
ENTPD2	NM_001246.4	c.1195G>C	p.Gly399Arg	missense_variant	Exon 8 of 9		NP_001237.1
ENTPD2	XM_011519212.3	c.955G>C	p.Gly319Arg	missense_variant	Exon 7 of 8		XP_011517514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD2	ENST00000355097.7	c.1264G>C	p.Gly422Arg	missense_variant	Exon 8 of 9	1	NM_203468.3	ENSP00000347213.2
ENTPD2	ENST00000312665.7	c.1195G>C	p.Gly399Arg	missense_variant	Exon 8 of 9	1		ENSP00000312494.5
ENTPD2	ENST00000460614.1	n.653G>C		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1380796 Hom.: 0 Cov.: 54 AF XY: 0.00 AC XY: 0 AN XY: 681020

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.30e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.4
DANN	Benign	0.66
DEOGEN2	Benign	0.0077	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.63	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.34	N;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.015
Sift	Benign	0.20	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.58		Loss of catalytic residue at V423 (P = 0.0202);.;
MVP		0.25
MPC		0.064
ClinPred		0.073	T
GERP RS		-0.52
Varity_R		0.14
gMVP		0.65

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139943413;