Genetic Variant PIK3C2A:c.*13T>C (chr11-17089725-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.820

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
PIK3C2A	NM_002645.4 link	c.*13T>C		3_prime_UTR_variant	Exon 33 of 33	ENST00000691414.1	NP_002636.2	O00443-1L7RRS0

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PIK3C2A	ENST00000691414 link	c.*13T>C	3_prime_UTR_variant	Exon 33 of 33		NM_002645.4	ENSP00000509400.1	O00443-1
PIK3C2A	ENST00000265970 link	c.*13T>C	3_prime_UTR_variant	Exon 32 of 32	1		ENSP00000265970.6	O00443-1
PIK3C2A	ENST00000531428.1 link	n.1400+1609T>C	intron_variant	Intron 12 of 12	1

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

87888

AN:

151858

Hom.:

25770

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.546

AC XY:

390012

AN XY:

713838

show subpopulations

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.:

AF XY:

0.580

AC XY:

43114

AN XY:

74284

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oculocerebrodental syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over