1-204446983-A-G

Position:

• chr1-204446983-A-G

Variant summary

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

The NM_001377334.1(PIK3C2B):​c.2489+453T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,104 control chromosomes in the GnomAD database, including 63,234 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 0.90 (63234 hom., cov: 30)
• Consequence: PIK3C2B NM_001377334.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44

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]

PIK3C2B (HGNC:):

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 = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIK3C2B	NM_001377334.1	c.2489+453T>C		intron_variant		ENST00000684373.1	NP_001364263.1
PIK3C2B	NM_002646.4	c.2489+453T>C		intron_variant			NP_002637.3
PIK3C2B	NM_001377335.1	c.2489+453T>C		intron_variant			NP_001364264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIK3C2B	ENST00000684373.1	c.2489+453T>C		intron_variant			NM_001377334.1	ENSP00000507222.1
PIK3C2B	ENST00000367187.7	c.2489+453T>C		intron_variant		1		ENSP00000356155.3
PIK3C2B	ENST00000424712.6	c.2489+453T>C		intron_variant		1		ENSP00000400561.2
PIK3C2B	ENST00000683234.1	n.1904+453T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137112 AN: 151986 Hom.: 63217 Cov.: 30

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.984

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.929

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

GnomAD4 genome AF: 0.902 AC: 137168 AN: 152104 Hom.: 63234 Cov.: 30 AF XY: 0.904 AC XY: 67234 AN XY: 74388

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.960

Gnomad4 ASJ AF: 0.984

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.958

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.996

Gnomad4 OTH AF: 0.929

Alfa AF: 0.939 Hom.: 7486

Bravo AF: 0.889

Asia WGS AF: 0.911 AC: 3171 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	0.14
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3106365; hg19: chr1-204416111;