7-106867947-ACCGGAGC-A

Variant names:

• chr7-106867947-ACCGGAGC-A
• NM_001282426.2:c.391_397delAGCCCGG

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001282426.2(PIK3CG):​c.391_397delAGCCCGG​(p.Ser131AlafsTer25) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as no classification for the single variant (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3CG NM_001282426.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23
• Publications: 0 publications found

Genes affected

PIK3CG (HGNC:8978): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma) Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I catalytic subunit of PI3K. Like other class I catalytic subunits (p110-alpha p110-beta, and p110-delta), the encoded protein binds a p85 regulatory subunit to form PI3K. This gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2015]

PIK3CG Gene-Disease associations (from GenCC):

• immunodeficiency 97 with autoinflammation

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282426.2. 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
	PIK3CG	NM_001282426.2	MANE Select	c.391_397delAGCCCGG	p.Ser131AlafsTer25	frameshift	Exon 2 of 11	NP_001269355.1	P48736
	PIK3CG	NM_001282427.2		c.391_397delAGCCCGG	p.Ser131AlafsTer25	frameshift	Exon 2 of 11	NP_001269356.1	P48736
	PIK3CG	NM_002649.3		c.391_397delAGCCCGG	p.Ser131AlafsTer25	frameshift	Exon 2 of 11	NP_002640.2	P48736

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3CG	ENST00000496166.6	TSL:1 MANE Select	c.391_397delAGCCCGG	p.Ser131AlafsTer25	frameshift	Exon 2 of 11	ENSP00000419260.1	P48736
	PIK3CG	ENST00000359195.3	TSL:1	c.391_397delAGCCCGG	p.Ser131AlafsTer25	frameshift	Exon 2 of 11	ENSP00000352121.3	P48736
	PIK3CG	ENST00000440650.6	TSL:1	c.391_397delAGCCCGG	p.Ser131AlafsTer25	frameshift	Exon 2 of 11	ENSP00000392258.2	P48736

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2

Splicing

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

Other links and lift over

hg19: chr7-106508392;