Variant 18-12009914-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000269159.8(IMPA2):c.262G>A(p.Ala88Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00327 in 1,614,102 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.017 ( 73 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 75 hom. )

Consequence

IMPA2
ENST00000269159.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.16

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029067397).

BP6

Variant 18-12009914-G-A is Benign according to our data. Variant chr18-12009914-G-A is described in ClinVar as [Benign]. Clinvar id is 788004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0579 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.262G>A	p.Ala88Thr	missense_variant	3/8	ENST00000269159.8	NP_055029.1
IMPA2	XM_011525659.4 linkuse as main transcript	c.214G>A	p.Ala72Thr	missense_variant	2/7		XP_011523961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPA2	ENST00000269159.8 linkuse as main transcript	c.262G>A	p.Ala88Thr	missense_variant	3/8	1	NM_014214.3	ENSP00000269159	P1	O14732-1

Frequencies

GnomAD3 genomes

AF:

0.0173

AC:

2626

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0599

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00616

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00470

AC:

1182

AN:

251414

Hom.:

AF XY:

0.00337

AC XY:

458

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.0622

Gnomad AMR exome

AF:

0.00312

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000369

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00181

AC:

2649

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1101

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0626

Gnomad4 AMR exome

AF:

0.00335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000138

Gnomad4 OTH exome

AF:

0.00374

GnomAD4 genome

AF:

0.0173

AC:

2631

AN:

152250

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1215

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0599

Gnomad4 AMR

AF:

0.00615

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00397

Hom.:

Bravo

AF:

0.0197

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0590

AC:

260

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00535

AC:

650

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.095

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.89

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.89

D;D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.58

REVEL

Benign

0.040

Sift

Benign

0.44

Sift4G

Benign

0.57

Polyphen

0.0040

Vest4

0.20

MVP

0.47

MPC

0.48

ClinPred

0.012

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.29

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

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