2-98544045-GCACACA-GCACACACA

Position:

• chr2-98544045-GCACACA-GCACACACA

Variant summary

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

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

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INPP4A	NM_001134225.2	c.949+56_949+57dupAC		intron_variant		ENST00000409851.8	NP_001127697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INPP4A	ENST00000409851.8	c.949+56_949+57dupAC		intron_variant		1	NM_001134225.2	ENSP00000386777.4

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

GnomAD3 exomes AF: 0.00237 AC: 256 AN: 107972 Hom.: 0 AF XY: 0.00251 AC XY: 143 AN XY: 56910

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 SAS exome AF: 0.00350

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

Gnomad4 AFR exome AF: 0.00197

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.000523

Gnomad4 EAS exome AF: 0.00143

Gnomad4 SAS exome AF: 0.00278

Gnomad4 FIN exome AF: 0.000389

Gnomad4 NFE exome AF: 0.00227

Gnomad4 OTH exome AF: 0.00290

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

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00231

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000584

Gnomad4 SAS AF: 0.000421

Gnomad4 FIN AF: 0.000194

Gnomad4 NFE AF: 0.00146

Gnomad4 OTH AF: 0.00336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3217304; hg19: chr2-99160508;