rs1044540301

Variant names:

• chr9-137048999-A-C
• NM_203468.3:c.1226T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-137048999-A-C
• chr9-137048999-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_203468.3(ENTPD2):​c.1226T>G​(p.Leu409Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,276 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. L409P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ENTPD2 NM_203468.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENTPD2	NM_203468.3	c.1226T>G	p.Leu409Arg	missense_variant	Exon 8 of 9	ENST00000355097.7	NP_982293.1
ENTPD2	NM_001246.4	c.1157T>G	p.Leu386Arg	missense_variant	Exon 8 of 9		NP_001237.1
ENTPD2	XM_011519212.3	c.917T>G	p.Leu306Arg	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.1226T>G	p.Leu409Arg	missense_variant	Exon 8 of 9	1	NM_203468.3	ENSP00000347213.2
ENTPD2	ENST00000312665.7	c.1157T>G	p.Leu386Arg	missense_variant	Exon 8 of 9	1		ENSP00000312494.5
ENTPD2	ENST00000460614.1	n.615T>G		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385276 Hom.: 0 Cov.: 67 AF XY: 0.00000146 AC XY: 1 AN XY: 683494

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;.
Eigen	Uncertain	0.41
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.85	T;T
M_CAP	Pathogenic	0.52	D
MetaRNN	Pathogenic	0.97	D;D
MetaSVM	Benign	-0.30	T
MutationAssessor	Pathogenic	3.8	H;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.99	D;D
Vest4		0.90
MutPred		0.92		Gain of methylation at L409 (P = 0.0169);.;
MVP		0.70
MPC		0.39
ClinPred		0.98	D
GERP RS		3.5
Varity_R		0.89
gMVP		0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139943451;