NM_014214.3:c.73C>G

Variant names:

• chr18-11981742-C-G
• rs1598677469
• NM_014214.3:c.73C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014214.3(IMPA2):​c.73C>G​(p.Gln25Glu) 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 benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: IMPA2 NM_014214.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13030848).

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.73C>G	p.Gln25Glu	missense	Exon 1 of 8	NP_055029.1	O14732-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMPA2	ENST00000269159.8	TSL:1 MANE Select	c.73C>G	p.Gln25Glu	missense	Exon 1 of 8	ENSP00000269159.3	O14732-1
	IMPA2	ENST00000383376.9	TSL:1	n.73C>G		non_coding_transcript_exon	Exon 1 of 7	ENSP00000372867.4	Q6PIP6
	IMPA2	ENST00000886600.1		c.73C>G	p.Gln25Glu	missense	Exon 1 of 6	ENSP00000556659.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Benign	0.87
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.91	N
PhyloP100		1.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.10	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.50		Loss of catalytic residue at Q25 (P = 0.0166)
MVP		0.38
MPC		0.57
ClinPred		0.087	T
GERP RS		3.1
PromoterAI		0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.20

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

Other links and lift over

dbSNP: rs1598677469; hg19: chr18-11981741;