Genetic Variant NM_203468.3:c.1177G>A (chr9-137049048-C-T) – ACMG Classification: Likely_benign (-2 pts)

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>A(p.Ala393Thr) 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. A393S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ENTPD2
NM_203468.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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=0.052476585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3 link	c.1177G>A	p.Ala393Thr	missense_variant	Exon 8 of 9	ENST00000355097.7	NP_982293.1	Q9Y5L3-1
ENTPD2	XM_011519212.3 link	c.868G>A	p.Ala290Thr	missense_variant	Exon 7 of 8		XP_011517514.1
ENTPD2	NM_001246.4 link	c.1150-42G>A		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>A	p.Ala393Thr	missense_variant	Exon 8 of 9	1	NM_203468.3	ENSP00000347213.2	Q9Y5L3-1
ENTPD2	ENST00000460614.1 link	n.566G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1
ENTPD2	ENST00000312665.7 link	c.1150-42G>A		intron_variant	Intron 7 of 8	1		ENSP00000312494.5	Q9Y5L3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1381902

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

681736

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:

0.00

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.9

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0085

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.62

M_CAP

Benign

0.0046

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.1

PhyloP100

-0.94

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.030

REVEL

Benign

0.0080

Sift

Benign

0.61

Sift4G

Benign

0.55

Polyphen

0.0080

Vest4

0.061

MutPred

0.38

Loss of MoRF binding (P = 0.1021);

MVP

0.25

MPC

0.056

ClinPred

0.032

GERP RS

0.13

Varity_R

0.052

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over