1-204482367-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377334.1(PIK3C2B):c.-85+11989A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,154 control chromosomes in the GnomAD database, including 31,302 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.62 (31302 hom., cov: 32)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

Genes affected

PIK3C2B (HGNC:8972): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta) The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is sensitive to low nanomolar levels of the inhibitor wortmanin. The C2 domain of this protein was shown to bind phospholipids but not Ca2+, which suggests that this enzyme may function in a calcium-independent manner. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3C2B	NM_001377334.1	c.-85+11989A>G		intron_variant		ENST00000684373.1
PIK3C2B	NM_001377335.1	c.-85+7449A>G		intron_variant
PIK3C2B	NM_002646.4	c.-85+7449A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3C2B	ENST00000684373.1	c.-85+11989A>G		intron_variant			NM_001377334.1	P1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94442 AN: 152036 Hom.: 31299 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.621

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.621 AC: 94463 AN: 152154 Hom.: 31302 Cov.: 32 AF XY: 0.627 AC XY: 46651 AN XY: 74370

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.616

Alfa AF: 0.696 Hom.: 8773

Bravo AF: 0.595

Asia WGS AF: 0.639 AC: 2221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	19
Dann	Benign	0.85

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: rs4951382; hg19: chr1-204451495;