rs7519417

Positions:

• chr1-204480824-T-C
• chr1-204480824-T-G

Variant summary

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

The NM_001377334.1(PIK3C2B):​c.-84-10938A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 151,890 control chromosomes in the GnomAD database, including 31,730 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 0.63 (31730 hom., cov: 30)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3C2B	NM_001377334.1	c.-84-10938A>G		intron_variant		ENST00000684373.1	NP_001364263.1
PIK3C2B	NM_001377335.1	c.-85+8992A>G		intron_variant			NP_001364264.1
PIK3C2B	NM_002646.4	c.-85+8992A>G		intron_variant			NP_002637.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3C2B	ENST00000684373.1	c.-84-10938A>G		intron_variant			NM_001377334.1	ENSP00000507222	P1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95290 AN: 151772 Hom.: 31728 Cov.: 30

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.625

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

GnomAD4 genome AF: 0.627 AC: 95311 AN: 151890 Hom.: 31730 Cov.: 30 AF XY: 0.634 AC XY: 47054 AN XY: 74238

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.620

Alfa AF: 0.699 Hom.: 8821

Bravo AF: 0.603

Asia WGS AF: 0.641 AC: 2227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.42
DANN	Benign	0.53

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: rs7519417; hg19: chr1-204449952;