rs1171963294

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_203468.3(ENTPD2):c.1177G>T(p.Ala393Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000196 in 1,534,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ENTPD2
NM_203468.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.941

Publications

0 publications found

Variant links:

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]

ENTPD2 links:

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ACMG classification

Classification was made for transcript

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=0.039155304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3 link	c.1177G>T	p.Ala393Ser	missense_variant	Exon 8 of 9	ENST00000355097.7	NP_982293.1	Q9Y5L3-1
ENTPD2	XM_011519212.3 link	c.868G>T	p.Ala290Ser	missense_variant	Exon 7 of 8		XP_011517514.1
ENTPD2	NM_001246.4 link	c.1150-42G>T		intron_variant	Intron 7 of 8		NP_001237.1	Q9Y5L3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENTPD2	ENST00000355097.7 link	c.1177G>T	p.Ala393Ser	missense_variant	Exon 8 of 9	1	NM_203468.3	ENSP00000347213.2	Q9Y5L3-1
ENTPD2	ENST00000460614.1 link	n.566G>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
ENTPD2	ENST00000312665.7 link	c.1150-42G>T		intron_variant	Intron 7 of 8	1		ENSP00000312494.5	Q9Y5L3-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD2 exomes

AF:

0.0000153

AC:

AN:

130592

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000972

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000203

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1381902

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

681736

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31272

American (AMR)

AF:

0.00

AC:

AN:

35250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25022

East Asian (EAS)

AF:

0.0000563

AC:

AN:

35512

South Asian (SAS)

AF:

0.00

AC:

AN:

79096

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35700

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5572

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076828

Other (OTH)

AF:

0.00

AC:

AN:

57650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 22, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1177G>T (p.A393S) alteration is located in exon 8 (coding exon 8) of the ENTPD2 gene. This alteration results from a G to T substitution at nucleotide position 1177, causing the alanine (A) at amino acid position 393 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.5

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.0088

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.63

M_CAP

Benign

0.0045

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.065

PhyloP100

-0.94

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.17

REVEL

Benign

0.0040

Sift

Benign

0.78

Sift4G

Benign

0.70

Polyphen

0.015

Vest4

0.053

MutPred

0.36

Gain of disorder (P = 0.0718);

MVP

0.22

MPC

0.052

ClinPred

0.017

GERP RS

0.13

Varity_R

0.066

gMVP

0.34

Mutation Taster

=99/1

polymorphism

(source)

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

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rs1171963294

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over