dbSNP rs750431257: IMPA2:p.Ala27Gly (chr18-11981749-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_014214.3(IMPA2):c.80C>G(p.Ala27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. A27V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IMPA2
NM_014214.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.815

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014214.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPA2	NM_014214.3	MANE Select	c.80C>G	p.Ala27Gly	missense	Exon 1 of 8	NP_055029.1	O14732-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IMPA2	ENST00000269159.8	TSL:1 MANE Select	c.80C>G	p.Ala27Gly	missense	Exon 1 of 8	ENSP00000269159.3	O14732-1
IMPA2	ENST00000383376.9	TSL:1	n.80C>G		non_coding_transcript_exon	Exon 1 of 7	ENSP00000372867.4	Q6PIP6
IMPA2	ENST00000886600.1		c.80C>G	p.Ala27Gly	missense	Exon 1 of 6	ENSP00000556659.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1076404

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

508490

African (AFR)

AF:

0.00

AC:

AN:

22736

American (AMR)

AF:

0.00

AC:

AN:

8282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14184

East Asian (EAS)

AF:

0.00

AC:

AN:

26294

South Asian (SAS)

AF:

0.00

AC:

AN:

19768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21088

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2922

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

917740

Other (OTH)

AF:

0.00

AC:

AN:

43390

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

0.0021

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.87

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

3.2

PhyloP100

1.9

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.033

Polyphen

0.85

Vest4

0.37

MutPred

0.78

Loss of stability (P = 0.0591)

MVP

0.52

MPC

0.63

ClinPred

0.99

GERP RS

4.0

PromoterAI

0.034

Neutral

(source)

Varity_R

0.84

gMVP

0.41

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over