The PIK3CA NM_006218.2:c.2015+9A>G (NP_006209.2:p.?) variant has been reported in ClinVar, where the aggregate classification is likely benign and the ClinGen Brain Malformations Variant Curation Expert Panel has classified it as likely benign.1 This variant is present in population databases at a frequency above the Brain Malformations VCEP BS1 threshold of 0.0185%, including 31/249678 alleles in gnomAD v2.1 (AF 0.01242%) and a highest observed African/African American frequency of 0.09391% in gnomAD v4.1.2 No variant-specific functional study was identified showing either an abnormal or a normal effect on PIK3CA splicing or function.3 Available computational splicing evidence could not be independently confirmed as a complete 2-of-3 benign prediction set, so BP4 and BP7 were not applied from the available records.4
PIK3CA
Final classification
Likely Benign
PIK3CA c.2015+9A>G · p.?
PIK3CA
The PIK3CA NM_006218.2:c.2015+9A>G (NP_006209.2:p.?) variant has been reported in ClinVar, where the aggregate classification is likely benign and the ClinGen Brain Malformations Variant Curation Expert Panel has classified it as likely benign.
Brain Malformations Specification Tavtigian point framework v1.1.0 point-based framework: BS1 strong (-4) = -4 points, which maps to Likely Benign.
Classification rationale
BS1BP6
Likely Benign
PIK3CA c.2015+9A>G
BS1 + BP6
→
Likely Benign
2
gnomad_v2 ↗gnomad_v4 ↗vcep_clingen_brainmalform_acmg_specifications_v1_1
3
cspec ↗
Gene diagram
· NM_006218.2 · variants mapped to exon structure
PIK3CA
NM_006218.2
Fetching transcript structure from UCSC…
Applied criteria · 2 met · select any tile
Met
Not met
Not assessed
N/A
Strength
very strong
supporting
Pathogenic evidence
PVS
PS
PM
PP
Benign evidence
BA
BS
BP
—
—
—
Rationale
Select a criterion.
Sources
Evidence used
Gaps remaining
Rule
—
Research & evidence
Population frequency · supports benign
gnomAD v4.1
gnomAD v2.1
v4.1
This variant is present in gnomAD v4.1 (AF= 5.80893e-05; MAF= 0.00581%, 90/1549338 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000939149; MAF= 0.09391%, 68/72406 alleles, homozygotes = 0); grpmax FAF= 0.00075934.
v2.1
This variant is present in gnomAD v2.1 (AF= 0.00012416; MAF= 0.01242%, 31/249678 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0.000859107; MAF= 0.08591%, 20/23280 alleles, homozygotes = 0); grpmax FAF= 0.00052743.
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
0.0058%
· 90 / 1,549,338
0 hom · FAF 0.076%
0 hom · FAF 0.076%
African/African American 68 / 72,406 |
0.094% |
Admixed American 10 / 50,446 |
0.02% |
Remaining individuals 5 / 59,892 |
0.0083% |
South Asian 1 / 82,454 |
0.0012% |
European (non-Finnish) 6 / 1,142,370 |
0.00053% |
+ 5 not observed (European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish)
gnomAD v2.1
0.012%
· 31 / 249,678
0 hom · FAF 0.053%
0 hom · FAF 0.053%
African/African American 20 / 23,280 |
0.086% |
Admixed American 9 / 26,068 |
0.035% |
Remaining individuals 1 / 6,166 |
0.016% |
European (non-Finnish) 1 / 119,282 |
0.00084% |
+ 4 not observed (Ashkenazi Jewish, East Asian, European (Finnish), South Asian)
ClinVar
This variant has been reported in ClinVar as Likely benign (1 clinical laboratory) and as Benign (1 clinical laboratory) and as Likely benign by ClinGen Brain Malformations Variant Curation Expert Panel (expert panel).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
No data
No calibrated functional assay or RNA evidence was identified for this variant.
COSMIC
Somatic evidence
COSMIC
This variant has not previously been reported in somatic cancers (COSMIC).
Hotspots
This variant does not lie in a statistically significant cancer hotspot.
Sources & reference links