Variant chr8-119564816-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001040092.3(ENPP2):c.2264+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00922 in 1,610,042 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0095 ( 85 hom. )

Consequence

ENPP2
NM_001040092.3 splice_region, intron

Scores

Splicing: ADA: 0.0001289

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.04

Variant links:

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]

ENPP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 8-119564816-C-T is Benign according to our data. Variant chr8-119564816-C-T is described in ClinVar as [Benign]. Clinvar id is 777833.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENPP2	NM_001040092.3 linkuse as main transcript	c.2264+7G>A		splice_region_variant, intron_variant		ENST00000075322.11	NP_001035181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENPP2	ENST00000075322.11 linkuse as main transcript	c.2264+7G>A		splice_region_variant, intron_variant		1	NM_001040092.3	ENSP00000075322	P1	Q13822-1

Frequencies

GnomAD3 genomes

AF:

0.00688

AC:

1045

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00148

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00754

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00303

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00594

AC:

1476

AN:

248460

Hom.:

AF XY:

0.00618

AC XY:

830

AN XY:

134378

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00280

Gnomad ASJ exome

AF:

0.00658

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00166

Gnomad FIN exome

AF:

0.00320

Gnomad NFE exome

AF:

0.00997

Gnomad OTH exome

AF:

0.00728

GnomAD4 exome

AF:

0.00946

AC:

13796

AN:

1457978

Hom.:

Cov.:

AF XY:

0.00924

AC XY:

6700

AN XY:

725360

show subpopulations

Gnomad4 AFR exome

AF:

0.00177

Gnomad4 AMR exome

AF:

0.00294

Gnomad4 ASJ exome

AF:

0.00721

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.00379

Gnomad4 NFE exome

AF:

0.0114

Gnomad4 OTH exome

AF:

0.00693

GnomAD4 genome

AF:

0.00687

AC:

1045

AN:

152064

Hom.:

Cov.:

AF XY:

0.00651

AC XY:

484

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.00754

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00303

Gnomad4 NFE

AF:

0.0115

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.00917

Hom.:

Bravo

AF:

0.00679

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.7

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over