rs747780229

Variant names:

• chr9-137048991-C-G
• rs747780229
• NM_203468.3:c.1234G>C

Your query was ambiguous. Multiple possible variants found:

• chr9-137048991-C-G
• chr9-137048991-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_203468.3(ENTPD2):​c.1234G>C​(p.Gly412Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,537,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: ENTPD2 NM_203468.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.55
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.895

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3	c.1234G>C	p.Gly412Arg	missense_variant	Exon 8 of 9	ENST00000355097.7	NP_982293.1
ENTPD2	NM_001246.4	c.1165G>C	p.Gly389Arg	missense_variant	Exon 8 of 9		NP_001237.1
ENTPD2	XM_011519212.3	c.925G>C	p.Gly309Arg	missense_variant	Exon 7 of 8		XP_011517514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTPD2	ENST00000355097.7	c.1234G>C	p.Gly412Arg	missense_variant	Exon 8 of 9	1	NM_203468.3	ENSP00000347213.2
ENTPD2	ENST00000312665.7	c.1165G>C	p.Gly389Arg	missense_variant	Exon 8 of 9	1		ENSP00000312494.5
ENTPD2	ENST00000460614.1	n.623G>C		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152182 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000682 AC: 9 AN: 131962 AF XY: 0.0000693

Gnomad AFR exome AF: 0.000166

Gnomad AMR exome AF: 0.000124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000613

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000103 AC: 143 AN: 1384892 Hom.: 0 Cov.: 68 AF XY: 0.000107 AC XY: 73 AN XY: 683172

African (AFR) AF: 0.0000320 AC: 1 AN: 31220

American (AMR) AF: 0.000141 AC: 5 AN: 35440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25048

East Asian (EAS) AF: 0.000310 AC: 11 AN: 35438

South Asian (SAS) AF: 0.00 AC: 0 AN: 79150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5562

European-Non Finnish (NFE) AF: 0.000112 AC: 121 AN: 1076966

Other (OTH) AF: 0.0000867 AC: 5 AN: 57696

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152298 Hom.: 0 Cov.: 34 AF XY: 0.0000537 AC XY: 4 AN XY: 74478

African (AFR) AF: 0.0000481 AC: 2 AN: 41560

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

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: 0.000132 AC: 9 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000672 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000598 AC: 5

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1234G>C (p.G412R) alteration is located in exon 8 (coding exon 8) of the ENTPD2 gene. This alteration results from a G to C substitution at nucleotide position 1234, causing the glycine (G) at amino acid position 412 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.0039	T
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Pathogenic	0.48	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Benign	-0.44	T
MutationAssessor	Pathogenic	3.5	H;.
PhyloP100		3.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-7.8	D;D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.82
MVP		0.58
MPC		0.38
ClinPred		0.98	D
GERP RS		3.2
Varity_R		0.89
gMVP		0.96
Mutation Taster		=25/75	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs747780229; hg19: chr9-139943443;