chr8-119570631-T-C

Variant names:

• chr8-119570631-T-C
• rs16892786
• NM_001040092.3:c.1917+74A>G

Variant summary

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

The NM_001040092.3(ENPP2):​c.1917+74A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 777,548 control chromosomes in the GnomAD database, including 5,785 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 0.12 (1182 hom., cov: 32)
  • Exomes 𝑓: 0.12 (4603 hom.)
• Consequence: ENPP2 NM_001040092.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENPP2	NM_001040092.3	c.1917+74A>G		intron_variant	Intron 20 of 24	ENST00000075322.11	NP_001035181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENPP2	ENST00000075322.11	c.1917+74A>G		intron_variant	Intron 20 of 24	1	NM_001040092.3	ENSP00000075322.6

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17838 AN: 152100 Hom.: 1179 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0515

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.115 AC: 71996 AN: 625330 Hom.: 4603 AF XY: 0.117 AC XY: 38081 AN XY: 325272

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0687

Gnomad4 ASJ exome AF: 0.142

Gnomad4 EAS exome AF: 0.0412

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.0953

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.117 AC: 17852 AN: 152218 Hom.: 1182 Cov.: 32 AF XY: 0.116 AC XY: 8622 AN XY: 74428

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0834

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0514

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0841

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.112

Alfa AF: 0.112 Hom.: 989

Bravo AF: 0.116

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.61
DANN	Benign	0.78

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: rs16892786; hg19: chr8-120582871;