18-12029858-A-G

Position:

• chr18-12029858-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014214.3(IMPA2):​c.752-485A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,210 control chromosomes in the GnomAD database, including 44,371 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44371 hom., cov: 33)
• Consequence: IMPA2 NM_014214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.70

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IMPA2	NM_014214.3	c.752-485A>G		intron_variant		ENST00000269159.8	NP_055029.1
IMPA2	XM_011525659.4	c.704-485A>G		intron_variant			XP_011523961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IMPA2	ENST00000269159.8	c.752-485A>G		intron_variant		1	NM_014214.3	ENSP00000269159.3

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115649 AN: 152092 Hom.: 44334 Cov.: 33

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.758

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.748

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.760 AC: 115741 AN: 152210 Hom.: 44371 Cov.: 33 AF XY: 0.761 AC XY: 56655 AN XY: 74414

Gnomad4 AFR AF: 0.821

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.758

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.750

Alfa AF: 0.734 Hom.: 28081

Bravo AF: 0.773

Asia WGS AF: 0.818 AC: 2846 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.057
DANN	Benign	0.32

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

LitVar

Other links and lift over

dbSNP: rs630110; hg19: chr18-12029857;