PIK3CA c.2188-7dupT, p.?
NM_006218.4:c.2188-7dupT
Likely Benign
The final classification of NM_006218.4:c.2188-7dupT in the PIK3CA gene is 'Likely Benign.' This classification is supported by multiple lines of evidence, including low population frequency (PM2), lack of significant splicing impact (BP4), and a benign report from a reputable source (BP6).
ACMG/AMP Criteria Applied
PM2
BP4
BP6
Genetic Information
Gene & Transcript Details
Gene
PIK3CA
Transcript
NM_006218.4
MANE Select
Total Exons
21
Strand
Forward (+)
Reference Sequence
NC_000003.11
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_006218.2 | Alternative | 21 exons | Forward |
| NM_006218.3 | Alternative | 21 exons | Forward |
Variant Details
HGVS Notation
NM_006218.4:c.2188-7dupT
Protein Change
?
Location
Exon 14i
(Exon 14i of 21)
5'Exon Structure (21 total)3'
Functional Consequence
Missense Variant
Related Variants
Variant interpretation based on transcript NM_006218.4
Genome Browser
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HGVS InputNM_006218:c.2188-7dupT
Active Tracks
ConservationRefSeqClinVargnomAD
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Clinical Data
Global Frequency
0.0233%
Low Frequency
Highest in Population
Ashkenazi Jewish
0.0616%
Common
Global: 0.0233%
Ashkenazi Jewish: 0.0616%
0%
0.05%
0.1%
1%
5%
10%+
Allele Information
Total: 240780Alt: 56Homozygotes: 0
ACMG Criteria Applied
PM2
This variant is common in the population (0.023300% MAF).
Classification
Benign
Based on 1 submitter review in ClinVar
Submitter Breakdown
1 B
Pathogenic
Likely Path.
VUS
Likely Benign
Benign
Publications (0)
No publication details.
Clinical Statement
This variant has been reported in ClinVar as Benign (1 clinical laboratories).
Functional Impact
Functional Domain
Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain (0 mutations).
Related Variants in This Domain
Computational Analysis
Pathogenicity Predictions
Predictor Consensus
Unknown
PP3 Applied
No
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific) VCEP Guidelines
PM2
PM2 (Supporting) Strength Modified
According to VCEP guidelines: 'Supporting Absent/rare from controls in an ethnically-matched cohort population sample (≥1).' The evidence for this variant shows: The variant has a minor allele frequency (MAF) of 0.0233% in gnomAD, indicating it is rare. Therefore, this criterion meets the requirements because the variant is present at a very low frequency in the population.
BP4
BP4 (Supporting)
According to VCEP guidelines: 'Award BP4 for a synonymous, intronic positions (except canonical splice sites) or non-coding variants in the UTRs, if two out of three of the splicing prediction tools predicted no impact on splicing function.' The evidence for this variant shows: SpliceAI analysis indicates a maximum score of 0.01 for acceptor loss, suggesting no significant effect on splicing function. Therefore, this criterion meets the requirements because the computational predictions indicate a lack of impact on splicing.
BP6
BP6 (Supporting)
According to VCEP guidelines: 'Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation.' The evidence for this variant shows: It has been reported as benign in ClinVar by one clinical laboratory. Therefore, this criterion meets the requirements because there is a reputable source supporting the benign classification.