NM_001282426.2:c.258C>A

Variant names:

• chr7-106867819-C-A
• rs530814976
• NM_001282426.2:c.258C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282426.2(PIK3CG):​c.258C>A​(p.Asp86Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PIK3CG NM_001282426.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06695098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CG	NM_001282426.2	c.258C>A	p.Asp86Glu	missense_variant	Exon 2 of 11	ENST00000496166.6	NP_001269355.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CG	ENST00000496166.6	c.258C>A	p.Asp86Glu	missense_variant	Exon 2 of 11	1	NM_001282426.2	ENSP00000419260.1
PIK3CG	ENST00000359195.3	c.258C>A	p.Asp86Glu	missense_variant	Exon 2 of 11	1		ENSP00000352121.3
PIK3CG	ENST00000440650.6	c.258C>A	p.Asp86Glu	missense_variant	Exon 2 of 11	1		ENSP00000392258.2
PIK3CG	ENST00000473541.5	c.-187+2393C>A		intron_variant	Intron 1 of 6	5		ENSP00000417623.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.48
DEOGEN2	Benign	0.16	T;T;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.73
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.56	.;.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.067	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.55	N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.070	N;N;N
REVEL	Benign	0.032
Sift	Benign	0.96	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.095
MutPred		0.33		Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);Gain of helix (P = 0.0128);
MVP		0.35
MPC		0.38
ClinPred		0.036	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.034
gMVP		0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs530814976; hg19: chr7-106508264;