Variant 18-11981751-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000269159.8(IMPA2):c.82C>G(p.Leu28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,076,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L28R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

IMPA2
ENST00000269159.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.498

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15473112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPA2	NM_014214.3 linkuse as main transcript	c.82C>G	p.Leu28Val	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.82C>G	p.Leu28Val	missense_variant	1/8	1	NM_014214.3	ENSP00000269159	P1	O14732-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000186

AC:

AN:

1076726

Hom.:

Cov.:

AF XY:

0.00000197

AC XY:

AN XY:

508656

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000218

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 16, 2021

The c.82C>G (p.L28V) alteration is located in exon 1 (coding exon 1) of the IMPA2 gene. This alteration results from a C to G substitution at nucleotide position 82, causing the leucine (L) at amino acid position 28 to be replaced by a valine (V). 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

0.097

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.27

T;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

.;L

MutationTaster

Benign

0.62

D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.74

.;N

REVEL

Benign

0.034

Sift

Benign

0.057

.;T

Sift4G

Benign

0.25

T;T

Polyphen

0.0

.;B

Vest4

0.24

MutPred

0.51

Loss of stability (P = 0.0818);Loss of stability (P = 0.0818);

MVP

0.30

MPC

0.46

ClinPred

0.18

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.44

gMVP

0.24

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