rs3217304

Variant names:

• chr2-98544045-GCACACACA-G
• rs3217304
• NM_001134225.2:c.949+50_949+57delACACACAC

Your query was ambiguous. Multiple possible variants found:

• chr2-98544045-GCACACACA-G
• chr2-98544045-GCACACACA-GCA
• chr2-98544045-GCACACACA-GCACA
• chr2-98544045-GCACACACA-GCACACA
• chr2-98544045-GCACACACA-GCACACACACA
• chr2-98544045-GCACACACA-GCACACACACACA
• chr2-98544045-GCACACACA-GCACACACACACACA
• chr2-98544045-GCACACACA-GCACACACACACACACA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001134225.2(INPP4A):​c.949+50_949+57delACACACAC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000155 in 1,290,988 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: INPP4A NM_001134225.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.508
• Publications: 0 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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP4A	NM_001134225.2	c.949+50_949+57delACACACAC		intron_variant	Intron 11 of 24	ENST00000409851.8	NP_001127697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP4A	ENST00000409851.8	c.949+39_949+46delCACACACA		intron_variant	Intron 11 of 24	1	NM_001134225.2	ENSP00000386777.4

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000155 AC: 2 AN: 1290988 Hom.: 0 AF XY: 0.00000314 AC XY: 2 AN XY: 636314

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

African (AFR) AF: 0.00 AC: 0 AN: 29574

American (AMR) AF: 0.00 AC: 0 AN: 33538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23022

East Asian (EAS) AF: 0.00 AC: 0 AN: 33562

South Asian (SAS) AF: 0.00 AC: 0 AN: 73078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5152

European-Non Finnish (NFE) AF: 0.00000100 AC: 1 AN: 995644

Other (OTH) AF: 0.0000187 AC: 1 AN: 53590

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.51

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;