Genetic Variant NM_203468.3:c.1234G>A (chr9-137048991-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_203468.3(ENTPD2):c.1234G>A(p.Gly412Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,384,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G412R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ENTPD2
NM_203468.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.55

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3 link	c.1234G>A	p.Gly412Ser	missense_variant	Exon 8 of 9	ENST00000355097.7	NP_982293.1	Q9Y5L3-1
ENTPD2	NM_001246.4 link	c.1165G>A	p.Gly389Ser	missense_variant	Exon 8 of 9		NP_001237.1	Q9Y5L3-2
ENTPD2	XM_011519212.3 link	c.925G>A	p.Gly309Ser	missense_variant	Exon 7 of 8		XP_011517514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENTPD2	ENST00000355097.7 link	c.1234G>A	p.Gly412Ser	missense_variant	Exon 8 of 9	1	NM_203468.3	ENSP00000347213.2	Q9Y5L3-1
ENTPD2	ENST00000312665.7 link	c.1165G>A	p.Gly389Ser	missense_variant	Exon 8 of 9	1		ENSP00000312494.5	Q9Y5L3-2
ENTPD2	ENST00000460614.1 link	n.623G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1384892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31220

American (AMR)

AF:

0.00

AC:

AN:

35440

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25048

East Asian (EAS)

AF:

0.00

AC:

AN:

35438

South Asian (SAS)

AF:

0.00

AC:

AN:

79150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5562

European-Non Finnish (NFE)

AF:

0.00000186

AC:

AN:

1076966

Other (OTH)

AF:

0.00

AC:

AN:

57696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.066

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

D;D

M_CAP

Pathogenic

0.33

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Benign

-0.74

MutationAssessor

Pathogenic

3.0

M;.

PhyloP100

3.6

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-5.8

D;D

REVEL

Uncertain

0.48

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

1.0

D;D

Vest4

0.76

MutPred

0.91

Gain of loop (P = 0.1069);.;

MVP

0.60

MPC

0.36

ClinPred

1.0

GERP RS

3.2

Varity_R

0.92

gMVP

0.90

Mutation Taster

=26/74

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_203468.3:c.1234G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over