2-98544045-GCACACACA-GCACACACACA

Variant names:

• chr2-98544045-G-GCA
• rs3217304
• NM_001134225.2:c.949+56_949+57dupAC

Variant summary

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

The NM_001134225.2(INPP4A):​c.949+56_949+57dupAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,435,952 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0022 (1 hom.)
• Consequence: INPP4A NM_001134225.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 4 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134225.2. 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
	INPP4A	NM_001134225.2	MANE Select	c.949+56_949+57dupAC		intron	N/A	NP_001127697.1	Q96PE3-3
	INPP4A	NM_001351425.2	MANE Plus Clinical	c.949+56_949+57dupAC		intron	N/A	NP_001338354.1	A0ABB0MUY6
	INPP4A	NM_001134224.2		c.949+56_949+57dupAC		intron	N/A	NP_001127696.1	Q96PE3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP4A	ENST00000409851.8	TSL:1 MANE Select	c.949+38_949+39insCA		intron	N/A	ENSP00000386777.4	Q96PE3-3
	INPP4A	ENST00000715854.1	MANE Plus Clinical	c.949+38_949+39insCA		intron	N/A	ENSP00000520526.1	A0ABB0MUY6
	INPP4A	ENST00000523221.2	TSL:1	c.949+38_949+39insCA		intron	N/A	ENSP00000427722.1	Q96PE3-1

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 203 AN: 150406 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00231

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000583

Gnomad SAS AF: 0.000420

Gnomad FIN AF: 0.000194

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00146

Gnomad OTH AF: 0.00339

GnomAD2 exomes AF: 0.00237 AC: 256 AN: 107972 AF XY: 0.00251

Gnomad AFR exome AF: 0.00236

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.00102

Gnomad EAS exome AF: 0.00252

Gnomad FIN exome AF: 0.000654

Gnomad NFE exome AF: 0.00252

Gnomad OTH exome AF: 0.00157

GnomAD4 exome AF: 0.00221 AC: 2838 AN: 1285436 Hom.: 1 Cov.: 0 AF XY: 0.00217 AC XY: 1375 AN XY: 633628

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00197 AC: 58 AN: 29426

American (AMR) AF: 0.00233 AC: 78 AN: 33422

Ashkenazi Jewish (ASJ) AF: 0.000523 AC: 12 AN: 22948

East Asian (EAS) AF: 0.00143 AC: 48 AN: 33474

South Asian (SAS) AF: 0.00278 AC: 202 AN: 72752

European-Finnish (FIN) AF: 0.000389 AC: 17 AN: 43676

Middle Eastern (MID) AF: 0.00311 AC: 16 AN: 5140

European-Non Finnish (NFE) AF: 0.00227 AC: 2252 AN: 991226

Other (OTH) AF: 0.00290 AC: 155 AN: 53372

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00136 AC: 205 AN: 150516 Hom.: 0 Cov.: 24 AF XY: 0.00133 AC XY: 98 AN XY: 73498

African (AFR) AF: 0.00135 AC: 55 AN: 40844

American (AMR) AF: 0.00231 AC: 35 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.000584 AC: 3 AN: 5134

South Asian (SAS) AF: 0.000421 AC: 2 AN: 4756

European-Finnish (FIN) AF: 0.000194 AC: 2 AN: 10316

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00146 AC: 99 AN: 67580

Other (OTH) AF: 0.00336 AC: 7 AN: 2086

Alfa AF: 0.00251 Hom.: 390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3217304; hg19: chr2-99160508;