Genetic Variant ENTPD2:p.Val480Ile (chr9-137048707-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_203468.3(ENTPD2):c.1438G>A(p.Val480Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000656 in 1,606,124 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

ENTPD2
NM_203468.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.64

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071597397).

BP6

Variant 9-137048707-C-T is Benign according to our data. Variant chr9-137048707-C-T is described in ClinVar as [Benign]. Clinvar id is 776479.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3 link	c.1438G>A	p.Val480Ile	missense_variant	Exon 9 of 9	ENST00000355097.7	NP_982293.1	Q9Y5L3-1
ENTPD2	NM_001246.4 link	c.1369G>A	p.Val457Ile	missense_variant	Exon 9 of 9		NP_001237.1	Q9Y5L3-2
ENTPD2	XM_011519212.3 link	c.1129G>A	p.Val377Ile	missense_variant	Exon 8 of 8		XP_011517514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENTPD2	ENST00000355097.7 link	c.1438G>A	p.Val480Ile	missense_variant	Exon 9 of 9	1	NM_203468.3	ENSP00000347213.2	Q9Y5L3-1
ENTPD2	ENST00000312665.7 link	c.1369G>A	p.Val457Ile	missense_variant	Exon 9 of 9	1		ENSP00000312494.5	Q9Y5L3-2
ENTPD2	ENST00000460614.1 link	n.827G>A		non_coding_transcript_exon_variant	Exon 2 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

532

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000934

AC:

216

AN:

231318

Hom.:

AF XY:

0.000649

AC XY:

AN XY:

126428

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.000389

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000196

Gnomad OTH exome

AF:

0.000707

GnomAD4 exome

AF:

0.000357

AC:

519

AN:

1453854

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

224

AN XY:

722666

show subpopulations

Gnomad4 AFR exome

AF:

0.0133

Gnomad4 AMR exome

AF:

0.000341

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.000850

GnomAD4 genome

AF:

0.00351

AC:

534

AN:

152270

Hom.:

Cov.:

AF XY:

0.00316

AC XY:

235

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0124

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000780

Hom.:

Bravo

AF:

0.00403

ESP6500AA

AF:

0.0110

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00115

AC:

139

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

9.5

DANN

Benign

0.87

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0072

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.061

Sift

Benign

0.67

T;T

Sift4G

Benign

0.70

T;T

Polyphen

0.12

B;B

Vest4

0.22

MVP

0.28

MPC

0.061

ClinPred

0.011

GERP RS

2.8

Varity_R

0.021

gMVP

0.47

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over