rs2699896

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006218.4(PIK3CA):c.1060-17C>A variant causes a 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 (★★). There are indicators that this mutation may affect the branch point..

Frequency

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

Exomes 𝑓: 0.57 ( 191188 hom. )

Consequence

PIK3CA
NM_006218.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.523

Publications

24 publications found

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 Gene-Disease associations (from GenCC):

overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
megalencephaly-capillary malformation-polymicrogyria syndrome
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
vascular malformation
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
Cowden disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Cowden syndrome 5
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

PIK3CA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but rather VUS (scored 4 / 10). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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 VariationId is 259957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
PIK3CA	NM_006218.4 link	c.1060-17C>A		intron_variant	Intron 5 of 20	ENST00000263967.4	NP_006209.2	P42336Q4LE51
PIK3CA	XM_006713658.5 link	c.1060-17C>A		intron_variant	Intron 5 of 20		XP_006713721.1	P42336Q4LE51

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIK3CA	ENST00000263967.4 link	c.1060-17C>A		intron_variant	Intron 5 of 20	2	NM_006218.4	ENSP00000263967.3		P42336

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

GnomAD2 exomes

AF:

0.555

AC:

137275

AN:

247268

AF XY:

0.555

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 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

African (AFR)

AF:

0.873

AC:

23677

AN:

27134

American (AMR)

AF:

0.496

AC:

21709

AN:

43786

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

14990

AN:

23850

East Asian (EAS)

AF:

0.241

AC:

9177

AN:

38060

South Asian (SAS)

AF:

0.565

AC:

44498

AN:

78812

European-Finnish (FIN)

AF:

0.483

AC:

25572

AN:

52948

Middle Eastern (MID)

AF:

0.678

AC:

3467

AN:

5114

European-Non Finnish (NFE)

AF:

0.585

AC:

479531

AN:

819474

Other (OTH)

AF:

0.576

AC:

28485

AN:

49454

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

12511

25022

37532

50043

62554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11536

23072

34608

46144

57680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.637

AC:

96864

AN:

152072

Hom.:

32593

Cov.:

AF XY:

0.627

AC XY:

46590

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.858

AC:

35611

AN:

41528

American (AMR)

AF:

0.548

AC:

8366

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

2151

AN:

3470

East Asian (EAS)

AF:

0.259

AC:

1338

AN:

5170

South Asian (SAS)

AF:

0.551

AC:

2655

AN:

4820

European-Finnish (FIN)

AF:

0.478

AC:

5029

AN:

10522

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.580

AC:

39426

AN:

67972

Other (OTH)

AF:

0.642

AC:

1359

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1658

3316

4974

6632

8290

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.614

Hom.:

9707

Bravo

AF:

0.653

Asia WGS

AF:

0.408

AC:

1417

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Jul 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cowden syndrome 5

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cowden syndrome

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.84

CADD

Benign

0.48

(source)

DANN

Benign

0.44

PhyloP100

-0.52

BranchPoint Hunter

4.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over