rs6594014

Variant names:

• chr1-204480306-A-G
• rs6594014
• NM_001377334.1:c.-84-10420T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377334.1(PIK3C2B):​c.-84-10420T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,066 control chromosomes in the GnomAD database, including 17,500 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 0.47 (17500 hom., cov: 32)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2B	NM_001377334.1	c.-84-10420T>C		intron_variant	Intron 1 of 32	ENST00000684373.1	NP_001364263.1
PIK3C2B	NM_002646.4	c.-85+9510T>C		intron_variant	Intron 3 of 34		NP_002637.3
PIK3C2B	NM_001377335.1	c.-85+9510T>C		intron_variant	Intron 3 of 35		NP_001364264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2B	ENST00000684373.1	c.-84-10420T>C		intron_variant	Intron 1 of 32		NM_001377334.1	ENSP00000507222.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71310 AN: 151950 Hom.: 17494 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.469 AC: 71340 AN: 152066 Hom.: 17500 Cov.: 32 AF XY: 0.474 AC XY: 35196 AN XY: 74324

African (AFR) AF: 0.333 AC: 13830 AN: 41498

American (AMR) AF: 0.526 AC: 8034 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1800 AN: 3472

East Asian (EAS) AF: 0.328 AC: 1692 AN: 5154

South Asian (SAS) AF: 0.439 AC: 2117 AN: 4820

European-Finnish (FIN) AF: 0.614 AC: 6489 AN: 10570

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35663 AN: 67954

Other (OTH) AF: 0.460 AC: 973 AN: 2116

Alfa AF: 0.510 Hom.: 16861

Bravo AF: 0.460

Asia WGS AF: 0.382 AC: 1329 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	1.6
DANN	Benign	0.28
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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: rs6594014; hg19: chr1-204449434;