Genetic Variant ENTPD2:c.1284+5G>A (chr9-137048936-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_203468.3(ENTPD2):c.1284+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00684 in 1,522,602 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 40 hom. )

Consequence

ENTPD2
NM_203468.3 splice_region, intron

Scores

Splicing: ADA: 0.9999

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.11

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 9-137048936-C-T is Benign according to our data. Variant chr9-137048936-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659795.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3 link	c.1284+5G>A	splice_region_variant, intron_variant	Intron 8 of 8	ENST00000355097.7	NP_982293.1	Q9Y5L3-1
ENTPD2	NM_001246.4 link	c.1215+5G>A	splice_region_variant, intron_variant	Intron 8 of 8		NP_001237.1	Q9Y5L3-2
ENTPD2	XM_011519212.3 link	c.975+5G>A	splice_region_variant, intron_variant	Intron 7 of 7		XP_011517514.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENTPD2	ENST00000355097.7 link	c.1284+5G>A	splice_region_variant, intron_variant	Intron 8 of 8	1	NM_203468.3	ENSP00000347213.2	Q9Y5L3-1
ENTPD2	ENST00000312665.7 link	c.1215+5G>A	splice_region_variant, intron_variant	Intron 8 of 8	1		ENSP00000312494.5	Q9Y5L3-2
ENTPD2	ENST00000460614.1 link	n.673+5G>A	splice_region_variant, intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.00463

AC:

704

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00863

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00353

AC:

427

AN:

120826

Hom.:

AF XY:

0.00332

AC XY:

221

AN XY:

66578

show subpopulations

Gnomad AFR exome

AF:

0.00210

Gnomad AMR exome

AF:

0.000973

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.00834

Gnomad OTH exome

AF:

0.00219

GnomAD4 exome

AF:

0.00708

AC:

9707

AN:

1370354

Hom.:

Cov.:

AF XY:

0.00681

AC XY:

4598

AN XY:

675324

show subpopulations

Gnomad4 AFR exome

AF:

0.00132

Gnomad4 AMR exome

AF:

0.000869

Gnomad4 ASJ exome

AF:

0.0000412

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000258

Gnomad4 FIN exome

AF:

0.00281

Gnomad4 NFE exome

AF:

0.00864

Gnomad4 OTH exome

AF:

0.00496

GnomAD4 genome

AF:

0.00462

AC:

704

AN:

152248

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

309

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00863

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00637

Hom.:

Bravo

AF:

0.00446

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ENTPD2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.050

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