Genetic Variant NM_014214.3:c.491A>G (chr18-12028043-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014214.3(IMPA2):c.491A>G(p.Asp164Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000689 in 1,451,614 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

IMPA2
NM_014214.3 missense, splice_region

Scores

Splicing: ADA: 0.001923

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.31

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:

ENSG00000293189 (HGNC:):

ENSG00000293189 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32800865).

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.491A>G	p.Asp164Gly	missense splice_region	Exon 6 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.491A>G	p.Asp164Gly	missense splice_region	Exon 6 of 8	ENSP00000269159.3	O14732-1
IMPA2	ENST00000588927.5	TSL:5	c.-77A>G		splice_region	Exon 6 of 8	ENSP00000464767.1	K7EII9
IMPA2	ENST00000589238.5	TSL:3	c.-77A>G		splice_region	Exon 6 of 8	ENSP00000465416.1	K7EII9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1451614

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722988

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33278

American (AMR)

AF:

0.00

AC:

AN:

44560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39646

South Asian (SAS)

AF:

0.00

AC:

AN:

86066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102772

Other (OTH)

AF:

0.00

AC:

AN:

60088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000370

Hom.:

Bravo

AF:

0.00000378

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

Benign

0.25

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

Eigen

Benign

-0.12

Eigen_PC

Benign

0.045

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

M_CAP

Benign

0.019

MetaRNN

Benign

0.33

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

5.3

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.0

REVEL

Benign

0.16

Sift

Benign

0.042

Sift4G

Uncertain

0.046

Polyphen

0.0060

Vest4

0.25

MutPred

0.40

Gain of MoRF binding (P = 0.0475)

MVP

0.62

MPC

0.63

ClinPred

0.98

GERP RS

5.8

Varity_R

0.53

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0019

dbscSNV1_RF

Benign

0.022

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

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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