rs7007970

Positions:

• chr8-119635689-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040092.3(ENPP2):​c.136+2736G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,172 control chromosomes in the GnomAD database, including 2,097 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2097 hom., cov: 33)
• Consequence: ENPP2 NM_001040092.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

Genes affected

ENPP2 (HGNC:3357): (ectonucleotide pyrophosphatase/phosphodiesterase 2) The protein encoded by this gene functions as both a phosphodiesterase, which cleaves phosphodiester bonds at the 5' end of oligonucleotides, and a phospholipase, which catalyzes production of lysophosphatidic acid (LPA) in extracellular fluids. LPA evokes growth factor-like responses including stimulation of cell proliferation and chemotaxis. This gene product stimulates the motility of tumor cells and has angiogenic properties, and its expression is upregulated in several kinds of carcinomas. The gene product is secreted and further processed to make the biologically active form. Several alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP2	NM_001040092.3	c.136+2736G>C		intron_variant		ENST00000075322.11	NP_001035181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP2	ENST00000075322.11	c.136+2736G>C		intron_variant		1	NM_001040092.3	ENSP00000075322	P1

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22544 AN: 152054 Hom.: 2094 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.0244

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.148 AC: 22562 AN: 152172 Hom.: 2097 Cov.: 33 AF XY: 0.148 AC XY: 10982 AN XY: 74394

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.0872

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.0245

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.132

Alfa AF: 0.114 Hom.: 631

Bravo AF: 0.150

Asia WGS AF: 0.0990 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.0
DANN	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs7007970; hg19: chr8-120647929;