chr9-137048707-C-T

Variant names:

• chr9-137048707-C-T
• rs139168222
• NM_203468.3:c.1438G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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. 14/21 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.64
• 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: Benign. The variant received -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	c.1438G>A	p.Val480Ile	missense_variant	Exon 9 of 9	ENST00000355097.7	NP_982293.1
ENTPD2	NM_001246.4	c.1369G>A	p.Val457Ile	missense_variant	Exon 9 of 9		NP_001237.1
ENTPD2	XM_011519212.3	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	Appris	UniProt
ENTPD2	ENST00000355097.7	c.1438G>A	p.Val480Ile	missense_variant	Exon 9 of 9	1	NM_203468.3	ENSP00000347213.2
ENTPD2	ENST00000312665.7	c.1369G>A	p.Val457Ile	missense_variant	Exon 9 of 9	1		ENSP00000312494.5
ENTPD2	ENST00000460614.1	n.827G>A		non_coding_transcript_exon_variant	Exon 2 of 2	1

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 532 AN: 152162 Hom.: 2 Cov.: 33

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

GnomAD2 exomes AF: 0.000934 AC: 216 AN: 231318 AF XY: 0.000649

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 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.: 2 Cov.: 39 AF XY: 0.000310 AC XY: 224 AN XY: 722666

African (AFR) AF: 0.0133 AC: 445 AN: 33388

American (AMR) AF: 0.000341 AC: 15 AN: 44018

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25840

East Asian (EAS) AF: 0.00 AC: 0 AN: 39528

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50978

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5746

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1109102

Other (OTH) AF: 0.000850 AC: 51 AN: 60034

GnomAD4 genome AF: 0.00351 AC: 534 AN: 152270 Hom.: 2 Cov.: 33 AF XY: 0.00316 AC XY: 235 AN XY: 74452

African (AFR) AF: 0.0124 AC: 516 AN: 41554

American (AMR) AF: 0.000849 AC: 13 AN: 15304

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00163 Hom.: 2

Bravo AF: 0.00403

ESP6500AA AF: 0.0110 AC: 48

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.00115 AC: 139

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.67	T
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	D
LIST_S2	Benign	0.57	T;T
MetaRNN	Benign	0.0072	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PhyloP100		1.6
PrimateAI	Uncertain	0.56	T
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	T
GERP RS		2.8
Varity_R		0.021
gMVP		0.47
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs139168222; hg19: chr9-139943159;