2-98467429-A-G

Variant names:

• chr2-98467429-A-G
• rs12617721
• NM_001134225.2:c.-166+22344A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001134225.2(INPP4A):​c.-166+22344A>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: INPP4A NM_001134225.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• Publications: 22 publications found

Genes affected

INPP4A (HGNC:6074): (inositol polyphosphate-4-phosphatase type I A) This gene encodes an Mg++ independent enzyme that hydrolyzes the 4-position phosphate from the inositol ring of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 3,4-bisphosphate. Multiple transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Aug 2008]

INPP4A Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4A	NM_001134225.2	c.-166+22344A>G		intron_variant	Intron 1 of 24	ENST00000409851.8	NP_001127697.1
INPP4A	NM_001351425.2	c.-166+22344A>G		intron_variant	Intron 1 of 25	ENST00000715854.1	NP_001338354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4A	ENST00000409851.8	c.-166+22344A>G		intron_variant	Intron 1 of 24	1	NM_001134225.2	ENSP00000386777.4
INPP4A	ENST00000715854.1	c.-166+22344A>G		intron_variant	Intron 1 of 25		NM_001351425.2	ENSP00000520526.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.68
PhyloP100		0.043

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: rs12617721; hg19: chr2-99083892;