18-11992726-T-C

Variant names:

• chr18-11992726-T-C
• rs589247
• NM_014214.3:c.97-6328T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014214.3(IMPA2):​c.97-6328T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,970 control chromosomes in the GnomAD database, including 13,107 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 0.39 (13107 hom., cov: 32)
• Consequence: IMPA2 NM_014214.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMPA2	NM_014214.3	c.97-6328T>C		intron_variant	Intron 1 of 7	ENST00000269159.8	NP_055029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPA2	ENST00000269159.8	c.97-6328T>C		intron_variant	Intron 1 of 7	1	NM_014214.3	ENSP00000269159.3

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58906 AN: 151852 Hom.: 13071 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.388 AC: 59006 AN: 151970 Hom.: 13107 Cov.: 32 AF XY: 0.392 AC XY: 29149 AN XY: 74284

African (AFR) AF: 0.586 AC: 24263 AN: 41436

American (AMR) AF: 0.325 AC: 4966 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 879 AN: 3466

East Asian (EAS) AF: 0.614 AC: 3161 AN: 5148

South Asian (SAS) AF: 0.487 AC: 2346 AN: 4816

European-Finnish (FIN) AF: 0.283 AC: 2995 AN: 10570

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19205 AN: 67950

Other (OTH) AF: 0.361 AC: 762 AN: 2110

Alfa AF: 0.323 Hom.: 3471

Bravo AF: 0.397

Asia WGS AF: 0.557 AC: 1935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.46
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs589247; hg19: chr18-11992725;