Variant 18-11981734-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000269159.8(IMPA2):c.65C>A(p.Ala22Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,229,378 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

IMPA2
ENST00000269159.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.512

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17630187).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPA2	NM_014214.3 linkuse as main transcript	c.65C>A	p.Ala22Glu	missense_variant	1/8	ENST00000269159.8	NP_055029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPA2	ENST00000269159.8 linkuse as main transcript	c.65C>A	p.Ala22Glu	missense_variant	1/8	1	NM_014214.3	ENSP00000269159	P1	O14732-1

Frequencies

GnomAD3 genomes

AF:

0.000559

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.000957

GnomAD4 exome

AF:

0.00109

AC:

1178

AN:

1077276

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

568

AN XY:

508958

show subpopulations

Gnomad4 AFR exome

AF:

0.000132

Gnomad4 AMR exome

AF:

0.000241

Gnomad4 ASJ exome

AF:

0.0000704

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000142

Gnomad4 NFE exome

AF:

0.00123

Gnomad4 OTH exome

AF:

0.000898

GnomAD4 genome

AF:

0.000559

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000763

Hom.:

Bravo

AF:

0.000544

ExAC

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.65C>A (p.A22E) alteration is located in exon 1 (coding exon 1) of the IMPA2 gene. This alteration results from a C to A substitution at nucleotide position 65, causing the alanine (A) at amino acid position 22 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.80

T;D

M_CAP

Pathogenic

0.56

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.86

.;L

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.96

.;N

REVEL

Benign

0.15

Sift

Benign

0.25

.;T

Sift4G

Benign

0.24

T;T

Polyphen

0.56

.;P

Vest4

0.34

MutPred

0.68

Loss of MoRF binding (P = 0.0659);Loss of MoRF binding (P = 0.0659);

MVP

0.48

MPC

1.4

ClinPred

0.51

GERP RS

-0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.29

gMVP

0.54

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