rs214901

Variant names:

• chr11-17206181-G-A
• rs214901
• NM_002645.4:c.-66+1667C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-17206181-G-A
• chr11-17206181-G-C
• chr11-17206181-G-T

Variant summary

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

The NM_002645.4(PIK3C2A):​c.-66+1667C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,998 control chromosomes in the GnomAD database, including 26,146 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 0.58 (26146 hom., cov: 33)
• Consequence: PIK3C2A NM_002645.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 7 publications found

Genes affected

PIK3C2A (HGNC:8971): (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha) 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 not sensitive to nanomolar levels of the inhibitor wortmanin. This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling. [provided by RefSeq, Jul 2008]

PIK3C2A Gene-Disease associations (from GenCC):

• oculocerebrodental syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIK3C2A	NM_002645.4	c.-66+1667C>T		intron_variant	Intron 1 of 32	ENST00000691414.1	NP_002636.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3C2A	ENST00000691414.1	c.-66+1667C>T		intron_variant	Intron 1 of 32		NM_002645.4	ENSP00000509400.1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88527 AN: 151880 Hom.: 26108 Cov.: 33

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.504

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.583 AC: 88624 AN: 151998 Hom.: 26146 Cov.: 33 AF XY: 0.585 AC XY: 43440 AN XY: 74298

African (AFR) AF: 0.624 AC: 25847 AN: 41452

American (AMR) AF: 0.631 AC: 9646 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2117 AN: 3470

East Asian (EAS) AF: 0.820 AC: 4249 AN: 5182

South Asian (SAS) AF: 0.613 AC: 2958 AN: 4822

European-Finnish (FIN) AF: 0.504 AC: 5298 AN: 10520

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.537 AC: 36495 AN: 67956

Other (OTH) AF: 0.612 AC: 1294 AN: 2114

Alfa AF: 0.559 Hom.: 4045

Bravo AF: 0.594

Asia WGS AF: 0.691 AC: 2404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.6
DANN	Benign	0.76
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs214901; hg19: chr11-17227728;