rs2699896

chr3-179204486-C-Achr3-179204486-C-G

Variant summary

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

The NM_006218.4(PIK3CA):c.1060-17C>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,290,704 control chromosomes in the GnomAD database, including 223,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 32593 hom., cov: 31)

Exomes 𝑓: 0.57 ( 191188 hom. )

Consequence

PIK3CA
NM_006218.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.523

Variant links:

Genes affected

PIK3CA (HGNC:8975): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]

PIK3CA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-179204486-C-A is Benign according to our data. Variant chr3-179204486-C-A is described in ClinVar as [Benign]. Clinvar id is 259957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-179204486-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4 linkuse as main transcript	c.1060-17C>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000263967.4
PIK3CA	XM_006713658.5 linkuse as main transcript	c.1060-17C>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4 linkuse as main transcript	c.1060-17C>A		splice_polypyrimidine_tract_variant, intron_variant		2	NM_006218.4	P1

Frequencies

GnomAD3 genomes

AF:

0.637

AC:

96765

AN:

151954

Hom.:

32547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.857

Gnomad AMI

AF:

0.793

Gnomad AMR

AF:

0.548

Gnomad ASJ

AF:

0.620

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.478

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.580

Gnomad OTH

AF:

0.647

GnomAD3 exomes

AF:

0.555

AC:

137275

AN:

247268

Hom.:

40044

AF XY:

0.555

AC XY:

74471

AN XY:

134178

show subpopulations

Gnomad AFR exome

AF:

0.865

Gnomad AMR exome

AF:

0.487

Gnomad ASJ exome

AF:

0.629

Gnomad EAS exome

AF:

0.263

Gnomad SAS exome

AF:

0.560

Gnomad FIN exome

AF:

0.486

Gnomad NFE exome

AF:

0.584

Gnomad OTH exome

AF:

0.575

GnomAD4 exome

AF:

0.572

AC:

651106

AN:

1138632

Hom.:

191188

Cov.:

AF XY:

0.571

AC XY:

332186

AN XY:

581320

show subpopulations

Gnomad4 AFR exome

AF:

0.873

Gnomad4 AMR exome

AF:

0.496

Gnomad4 ASJ exome

AF:

0.629

Gnomad4 EAS exome

AF:

0.241

Gnomad4 SAS exome

AF:

0.565

Gnomad4 FIN exome

AF:

0.483

Gnomad4 NFE exome

AF:

0.585

Gnomad4 OTH exome

AF:

0.576

GnomAD4 genome

AF:

0.637

AC:

96864

AN:

152072

Hom.:

32593

Cov.:

AF XY:

0.627

AC XY:

46590

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.858

Gnomad4 AMR

AF:

0.548

Gnomad4 ASJ

AF:

0.620

Gnomad4 EAS

AF:

0.259

Gnomad4 SAS

AF:

0.551

Gnomad4 FIN

AF:

0.478

Gnomad4 NFE

AF:

0.580

Gnomad4 OTH

AF:

0.642

Alfa

AF:

0.611

Hom.:

5421

Bravo

AF:

0.653

Asia WGS

AF:

0.408

AC:

1417

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Cowden syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Cowden syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

0.48

Dann

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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