chr18-11981745-C-G

Position:

• chr18-11981745-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000269159.8(IMPA2):​c.76C>G​(p.Leu26Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000929 in 1,076,914 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: IMPA2 ENST00000269159.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.187

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

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=0.17043006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPA2	NM_014214.3	c.76C>G	p.Leu26Val	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	c.76C>G	p.Leu26Val	missense_variant	1/8	1	NM_014214.3	ENSP00000269159	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.29e-7 AC: 1 AN: 1076914 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 508752

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: 0.00000109

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 16, 2021

The c.76C>G (p.L26V) 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 76, causing the leucine (L) at amino acid position 26 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	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.85	D;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.17	.;N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.33	.;N
REVEL	Benign	0.069
Sift	Benign	0.36	.;T
Sift4G	Benign	0.27	T;T
Polyphen		0.050	.;B
Vest4		0.27
MutPred		0.73		Gain of MoRF binding (P = 0.0868);Gain of MoRF binding (P = 0.0868);
MVP		0.33
MPC		0.47
ClinPred		0.20	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-11981744;