rs200768351
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP7BS1BP4
This summary comes from the ClinGen Evidence Repository: The c.2015+9A>G (NM_006218.4) variant in PIK3CA is an intronic variant. The highest population minor allele frequency in gnomAD v2.1.1 is 0.0008591 in the African/African American population, which is higher than the ClinGen BMEP threshold ([>0.00037]) for BS1, and therefore meets this criterion (BS1). The results from in silico splicing predictors MaxEntScan, spliceAI and varSEAK support that this variant does not affect splicing (BP4). This variant is a synonymous (silent) variant that occurs at a nucleotide that is not conserved according to a PhyloP <0.1 (BP7). In summary, this variant meets the criteria to be classified as Likely benign for mosaic autosomal dominant overgrowth with or without cerebral malformations due to abnormalities in MTOR-pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen Brain Malformations Expert Panel: BS1, BP4, BP7; -6 points (VCEP specifications version 1; Approved: 1/31/2021) LINK:https://erepo.genome.network/evrepo/ui/classification/CA2710843/MONDO:0016054/018
Frequency
Consequence
NM_006218.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PIK3CA | NM_006218.4 | c.2015+9A>G | intron_variant | ENST00000263967.4 | |||
PIK3CA | XM_006713658.5 | c.2015+9A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PIK3CA | ENST00000263967.4 | c.2015+9A>G | intron_variant | 2 | NM_006218.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000316 AC: 48AN: 151978Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000110 AC: 24AN: 218450Hom.: 0 AF XY: 0.0000586 AC XY: 7AN XY: 119426
GnomAD4 exome AF: 0.0000301 AC: 42AN: 1397242Hom.: 0 Cov.: 26 AF XY: 0.0000144 AC XY: 10AN XY: 694706
GnomAD4 genome ? AF: 0.000316 AC: 48AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24AN XY: 74364
ClinVar
Submissions by phenotype
Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen Brain Malformations Variant Curation Expert Panel | Feb 12, 2022 | The c.2015+9A>G (NM_006218.4) variant in PIK3CA is an intronic variant. The highest population minor allele frequency in gnomAD v2.1.1 is 0.0008591 in the African/African American population, which is higher than the ClinGen BMEP threshold ([>0.00037]) for BS1, and therefore meets this criterion (BS1). The results from in silico splicing predictors MaxEntScan, spliceAI and varSEAK support that this variant does not affect splicing (BP4). This variant is a synonymous (silent) variant that occurs at a nucleotide that is not conserved according to a PhyloP <0.1 (BP7). In summary, this variant meets the criteria to be classified as Likely benign for mosaic autosomal dominant overgrowth with or without cerebral malformations due to abnormalities in MTOR-pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen Brain Malformations Expert Panel: BS1, BP4, BP7; -6 points (VCEP specifications version 1; Approved: 1/31/2021) - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 08, 2020 | - - |
Cowden syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at