9-137048964-C-T

Variant names:

• chr9-137048964-C-T
• rs1376642191
• NM_203468.3:c.1261G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203468.3(ENTPD2):​c.1261G>A​(p.Gly421Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. G421R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ENTPD2 NM_203468.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02943474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3	c.1261G>A	p.Gly421Ser	missense_variant	Exon 8 of 9	ENST00000355097.7	NP_982293.1
ENTPD2	NM_001246.4	c.1192G>A	p.Gly398Ser	missense_variant	Exon 8 of 9		NP_001237.1
ENTPD2	XM_011519212.3	c.952G>A	p.Gly318Ser	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.1261G>A	p.Gly421Ser	missense_variant	Exon 8 of 9	1	NM_203468.3	ENSP00000347213.2
ENTPD2	ENST00000312665.7	c.1192G>A	p.Gly398Ser	missense_variant	Exon 8 of 9	1		ENSP00000312494.5
ENTPD2	ENST00000460614.1	n.650G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.012
DANN	Benign	0.91
DEOGEN2	Benign	0.0075	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.029	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.40	N;.
PhyloP100		-2.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.89	N;N
REVEL	Benign	0.010
Sift	Benign	0.40	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.062	B;B
Vest4		0.046
MutPred		0.43		Gain of glycosylation at G421 (P = 0.0166);.;
MVP		0.15
MPC		0.055
ClinPred		0.17	T
GERP RS		-6.9
Varity_R		0.026
gMVP		0.52
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1376642191; hg19: chr9-139943416;