7-106868118-C-A

Variant names:

• chr7-106868118-C-A
• NM_001282426.2:c.557C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001282426.2(PIK3CG):​c.557C>A​(p.Ala186Glu) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3CG NM_001282426.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.69

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14638412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CG	NM_001282426.2	c.557C>A	p.Ala186Glu	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.557C>A	p.Ala186Glu	missense_variant	Exon 2 of 11	1	NM_001282426.2	ENSP00000419260.1
PIK3CG	ENST00000359195.3	c.557C>A	p.Ala186Glu	missense_variant	Exon 2 of 11	1		ENSP00000352121.3
PIK3CG	ENST00000440650.6	c.557C>A	p.Ala186Glu	missense_variant	Exon 2 of 11	1		ENSP00000392258.2
PIK3CG	ENST00000473541.5	c.-187+2692C>A		intron_variant	Intron 1 of 6	5		ENSP00000417623.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Mar 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.557C>A (p.A186E) alteration is located in exon 2 (coding exon 1) of the PIK3CG gene. This alteration results from a C to A substitution at nucleotide position 557, causing the alanine (A) at amino acid position 186 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.39
DEOGEN2	Benign	0.15	T;T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.96	.;.;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L;L;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.43	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.60	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0070	B;B;B
Vest4		0.30
MutPred		0.43		Gain of disorder (P = 0.0188);Gain of disorder (P = 0.0188);Gain of disorder (P = 0.0188);
MVP		0.35
MPC		0.51
ClinPred		0.13	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Varity_R		0.15
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-106508563;