1-9718862-G-C

Variant names:

• chr1-9718862-G-C
• rs571644641
• NM_005026.5:c.1189G>C

Variant summary

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

The NM_005026.5(PIK3CD):​c.1189G>C​(p.Val397Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V397M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PIK3CD NM_005026.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.90
• Publications: 1 publications found

Genes affected

PIK3CD (HGNC:8977): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta) Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I PI3K found primarily in leukocytes. Like other class I PI3Ks (p110-alpha p110-beta, and p110-gamma), the encoded protein binds p85 adapter proteins and GTP-bound RAS. However, unlike the other class I PI3Ks, this protein phosphorylates itself, not p85 protein.[provided by RefSeq, Jul 2010]

PIK3CD Gene-Disease associations (from GenCC):

• immunodeficiency 14

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• immunodeficiency 14b, autosomal recessive

  Inheritance: AR, Unknown Classification: DEFINITIVE, MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• activated PI3K-delta syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC124903839 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3CD	NM_005026.5	c.1189G>C	p.Val397Leu	missense_variant	Exon 9 of 24	ENST00000377346.9	NP_005017.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CD	ENST00000377346.9	c.1189G>C	p.Val397Leu	missense_variant	Exon 9 of 24	1	NM_005026.5	ENSP00000366563.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	.;T;D;.;T
Eigen	Benign	0.13
Eigen_PC	Benign	0.065
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D;D;D;.
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.69	D;D;D;D;D
MetaSVM	Uncertain	-0.045	T
MutationAssessor	Uncertain	2.1	.;.;M;.;.
PhyloP100		6.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.9	N;.;N;.;N
REVEL	Uncertain	0.57
Sift	Benign	0.11	T;.;T;.;T
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.74	P;.;P;P;.
Vest4		0.50
MutPred		0.69		Loss of methylation at K365 (P = 0.0724);Loss of methylation at K365 (P = 0.0724);.;Loss of methylation at K365 (P = 0.0724);Loss of methylation at K365 (P = 0.0724);
MVP		0.85
MPC		1.4
ClinPred		0.88	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.88
Mutation Taster		=63/37	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: rs571644641; hg19: chr1-9778920;