chr8-119560645-C-T

Variant names:

• chr8-119560645-C-T
• rs6982484
• NM_001040092.3:c.2421+2212G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040092.3(ENPP2):​c.2421+2212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,044 control chromosomes in the GnomAD database, including 7,056 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 0.30 (7056 hom., cov: 32)
• Consequence: ENPP2 NM_001040092.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.85
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENPP2	NM_001040092.3	c.2421+2212G>A		intron_variant	Intron 24 of 24	ENST00000075322.11	NP_001035181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP2	ENST00000075322.11	c.2421+2212G>A		intron_variant	Intron 24 of 24	1	NM_001040092.3	ENSP00000075322.6

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45375 AN: 151926 Hom.: 7049 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.299 AC: 45402 AN: 152044 Hom.: 7056 Cov.: 32 AF XY: 0.306 AC XY: 22776 AN XY: 74326

African (AFR) AF: 0.290 AC: 12011 AN: 41476

American (AMR) AF: 0.361 AC: 5516 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3470

East Asian (EAS) AF: 0.377 AC: 1950 AN: 5174

South Asian (SAS) AF: 0.402 AC: 1933 AN: 4814

European-Finnish (FIN) AF: 0.374 AC: 3940 AN: 10548

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18489 AN: 67976

Other (OTH) AF: 0.267 AC: 564 AN: 2112

Alfa AF: 0.307 Hom.: 1247

Bravo AF: 0.293

Asia WGS AF: 0.398 AC: 1383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.21
DANN	Benign	0.64
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs6982484; hg19: chr8-120572885;