chr7-106867982-C-G

Variant names:

• chr7-106867982-C-G
• rs367817179
• NM_001282426.2:c.421C>G

Variant summary

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

The NM_001282426.2(PIK3CG):​c.421C>G​(p.His141Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: PIK3CG NM_001282426.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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=0.078080654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CG	NM_001282426.2	c.421C>G	p.His141Asp	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.421C>G	p.His141Asp	missense_variant	Exon 2 of 11	1	NM_001282426.2	ENSP00000419260.1
PIK3CG	ENST00000359195.3	c.421C>G	p.His141Asp	missense_variant	Exon 2 of 11	1		ENSP00000352121.3
PIK3CG	ENST00000440650.6	c.421C>G	p.His141Asp	missense_variant	Exon 2 of 11	1		ENSP00000392258.2
PIK3CG	ENST00000473541.5	c.-187+2556C>G		intron_variant	Intron 1 of 6	5		ENSP00000417623.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152220 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74380

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T;T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.47	.;.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.078	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.030	N;N;N
REVEL	Benign	0.066
Sift	Benign	0.29	T;T;T
Sift4G	Benign	0.53	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.23
MutPred		0.18		Gain of relative solvent accessibility (P = 0.0999);Gain of relative solvent accessibility (P = 0.0999);Gain of relative solvent accessibility (P = 0.0999);
MVP		0.31
MPC		0.57
ClinPred		0.071	T
GERP RS		3.7
Varity_R		0.097
gMVP		0.29

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: rs367817179; hg19: chr7-106508427;