rs6692377

Variant names:

• chr1-204480029-G-A
• rs6692377
• NM_001377334.1:c.-84-10143C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-204480029-G-A
• chr1-204480029-G-C
• chr1-204480029-G-T

Variant summary

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

The NM_001377334.1(PIK3C2B):​c.-84-10143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,100 control chromosomes in the GnomAD database, including 16,907 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 0.46 (16907 hom., cov: 33)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.470
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377334.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2B	NM_001377334.1	MANE Select	c.-84-10143C>T		intron	N/A	NP_001364263.1	O00750
	PIK3C2B	NM_002646.4		c.-85+9787C>T		intron	N/A	NP_002637.3
	PIK3C2B	NM_001377335.1		c.-85+9787C>T		intron	N/A	NP_001364264.1	F5GWN5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIK3C2B	ENST00000684373.1	MANE Select	c.-84-10143C>T		intron	N/A	ENSP00000507222.1	O00750
	PIK3C2B	ENST00000367187.7	TSL:1	c.-85+9787C>T		intron	N/A	ENSP00000356155.3	O00750
	PIK3C2B	ENST00000424712.6	TSL:1	c.-85+9787C>T		intron	N/A	ENSP00000400561.2	F5GWN5

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69592 AN: 151982 Hom.: 16897 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.615

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.458 AC: 69630 AN: 152100 Hom.: 16907 Cov.: 33 AF XY: 0.462 AC XY: 34400 AN XY: 74380

African (AFR) AF: 0.301 AC: 12493 AN: 41506

American (AMR) AF: 0.518 AC: 7930 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1788 AN: 3468

East Asian (EAS) AF: 0.314 AC: 1616 AN: 5152

South Asian (SAS) AF: 0.436 AC: 2104 AN: 4826

European-Finnish (FIN) AF: 0.615 AC: 6503 AN: 10582

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.523 AC: 35517 AN: 67952

Other (OTH) AF: 0.451 AC: 953 AN: 2112

Alfa AF: 0.485 Hom.: 11606

Bravo AF: 0.446

Asia WGS AF: 0.365 AC: 1271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.73
PhyloP100		0.47
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: rs6692377; hg19: chr1-204449157;