11-17089725-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002645.4(PIK3C2A):c.*13T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 1,585,344 control chromosomes in the GnomAD database, including 241,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (25813 hom., cov: 32)
  • Exomes 𝑓: 0.54 (215999 hom.)
• Consequence: PIK3C2A NM_002645.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.820

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-17089725-A-G is Benign according to our data. Variant chr11-17089725-A-G is described in ClinVar as [Benign]. Clinvar id is 1327026.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3C2A	NM_002645.4	c.*13T>C		3_prime_UTR_variant	33/33	ENST00000691414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3C2A	ENST00000691414.1	c.*13T>C		3_prime_UTR_variant	33/33		NM_002645.4	P1
PIK3C2A	ENST00000265970.11	c.*13T>C		3_prime_UTR_variant	32/32	1		P1
PIK3C2A	ENST00000531428.1	n.1400+1609T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87888 AN: 151858 Hom.: 25770 Cov.: 32

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.614

GnomAD3 exomes AF: 0.590 AC: 146465 AN: 248242 Hom.: 44134 AF XY: 0.587 AC XY: 78827 AN XY: 134204

Gnomad AFR exome AF: 0.624

Gnomad AMR exome AF: 0.653

Gnomad ASJ exome AF: 0.600

Gnomad EAS exome AF: 0.838

Gnomad SAS exome AF: 0.601

Gnomad FIN exome AF: 0.508

Gnomad NFE exome AF: 0.538

Gnomad OTH exome AF: 0.585

GnomAD4 exome AF: 0.544 AC: 780043 AN: 1433368 Hom.: 215999 Cov.: 25 AF XY: 0.546 AC XY: 390012 AN XY: 713838

Gnomad4 AFR exome AF: 0.621

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.607

Gnomad4 EAS exome AF: 0.821

Gnomad4 SAS exome AF: 0.602

Gnomad4 FIN exome AF: 0.509

Gnomad4 NFE exome AF: 0.522

Gnomad4 OTH exome AF: 0.569

GnomAD4 genome AF: 0.579 AC: 87992 AN: 151976 Hom.: 25813 Cov.: 32 AF XY: 0.580 AC XY: 43114 AN XY: 74284

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.614

Alfa AF: 0.557 Hom.: 23969

Bravo AF: 0.591

Asia WGS AF: 0.685 AC: 2384 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Oculocerebrodental syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	13
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: rs10832733; hg19: chr11-17111272; COSMIC: COSV56400085;