Variant chr18-12009876-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000269159.8(IMPA2):c.231-7A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,610,408 control chromosomes in the GnomAD database, including 178 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 0.019 ( 89 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 89 hom. )

Consequence

IMPA2
ENST00000269159.8 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0005307

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0310

Variant links:

Genes affected

IMPA2 (HGNC:6051): (inositol monophosphatase 2) This locus encodes an inositol monophosphatase. The encoded protein catalyzes the dephosphoylration of inositol monophosphate and plays an important role in phosphatidylinositol signaling. This locus may be associated with susceptibility to bipolar disorder. [provided by RefSeq, Jan 2011]

IMPA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 18-12009876-A-G is Benign according to our data. Variant chr18-12009876-A-G is described in ClinVar as [Benign]. Clinvar id is 788910.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPA2	NM_014214.3 linkuse as main transcript	c.231-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000269159.8	NP_055029.1
IMPA2	XM_011525659.4 linkuse as main transcript	c.183-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_011523961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPA2	ENST00000269159.8 linkuse as main transcript	c.231-7A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014214.3	ENSP00000269159	P1	O14732-1

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2892

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0665

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00603

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00458

AC:

1151

AN:

251142

Hom.:

AF XY:

0.00333

AC XY:

452

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.0633

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000793

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00193

AC:

2809

AN:

1458278

Hom.:

Cov.:

AF XY:

0.00165

AC XY:

1198

AN XY:

725608

show subpopulations

Gnomad4 AFR exome

AF:

0.0674

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000559

Gnomad4 OTH exome

AF:

0.00416

GnomAD4 genome

AF:

0.0191

AC:

2904

AN:

152130

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1365

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0666

Gnomad4 AMR

AF:

0.00602

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0126

Hom.:

Bravo

AF:

0.0211

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

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 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.7

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00053

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.080

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