7-106867796-C-G

Variant names:

• chr7-106867796-C-G
• rs763784435
• NM_001282426.2:c.235C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282426.2(PIK3CG):​c.235C>G​(p.Leu79Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L79M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PIK3CG NM_001282426.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10639241).

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.235C>G	p.Leu79Val	missense	Exon 2 of 11	NP_001269355.1	P48736
	PIK3CG	NM_001282427.2		c.235C>G	p.Leu79Val	missense	Exon 2 of 11	NP_001269356.1	P48736
	PIK3CG	NM_002649.3		c.235C>G	p.Leu79Val	missense	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.235C>G	p.Leu79Val	missense	Exon 2 of 11	ENSP00000419260.1	P48736
	PIK3CG	ENST00000359195.3	TSL:1	c.235C>G	p.Leu79Val	missense	Exon 2 of 11	ENSP00000352121.3	P48736
	PIK3CG	ENST00000440650.6	TSL:1	c.235C>G	p.Leu79Val	missense	Exon 2 of 11	ENSP00000392258.2	P48736

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460340 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726574

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111912

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.54
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.077
Sift	Benign	0.62	T
Sift4G	Benign	0.80	T
Polyphen		0.0	B
Vest4		0.065
MutPred		0.33		Loss of stability (P = 0.0861)
MVP		0.28
MPC		0.41
ClinPred		0.039	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.044
gMVP		0.20
Mutation Taster		=91/9	polymorphism

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: rs763784435; hg19: chr7-106508241;