rs373169384

Variant names:

• chr9-137048936-C-T
• rs373169384
• NM_203468.3:c.1284+5G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PP3_Moderate BP6_Moderate BS2

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
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
• 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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3	c.1284+5G>A		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000355097.7	NP_982293.1
ENTPD2	NM_001246.4	c.1215+5G>A		splice_region_variant, intron_variant	Intron 8 of 8		NP_001237.1
ENTPD2	XM_011519212.3	c.975+5G>A		splice_region_variant, intron_variant	Intron 7 of 7		XP_011517514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD2	ENST00000355097.7	c.1284+5G>A		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_203468.3	ENSP00000347213.2
ENTPD2	ENST00000312665.7	c.1215+5G>A		splice_region_variant, intron_variant	Intron 8 of 8	1		ENSP00000312494.5
ENTPD2	ENST00000460614.1	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.: 3 Cov.: 33

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

GnomAD2 exomes AF: 0.00353 AC: 427 AN: 120826 AF XY: 0.00332

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 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.: 40 Cov.: 48 AF XY: 0.00681 AC XY: 4598 AN XY: 675324

African (AFR) AF: 0.00132 AC: 40 AN: 30292

American (AMR) AF: 0.000869 AC: 28 AN: 32222

Ashkenazi Jewish (ASJ) AF: 0.0000412 AC: 1 AN: 24272

East Asian (EAS) AF: 0.00 AC: 0 AN: 35188

South Asian (SAS) AF: 0.0000258 AC: 2 AN: 77590

European-Finnish (FIN) AF: 0.00281 AC: 109 AN: 38832

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5172

European-Non Finnish (NFE) AF: 0.00864 AC: 9245 AN: 1069882

Other (OTH) AF: 0.00496 AC: 282 AN: 56904

GnomAD4 genome AF: 0.00462 AC: 704 AN: 152248 Hom.: 3 Cov.: 33 AF XY: 0.00415 AC XY: 309 AN XY: 74432

African (AFR) AF: 0.00149 AC: 62 AN: 41562

American (AMR) AF: 0.00203 AC: 31 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00188 AC: 20 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00863 AC: 587 AN: 67980

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00637 Hom.: 3

Bravo AF: 0.00446

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	19
DANN	Benign	0.95
PhyloP100		1.1
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs373169384; hg19: chr9-139943388;