rs201370957
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: The c.160G>A (NM_005027.4) variant in PIK3R2 is a missense variant predicted to cause substitution of (p.Val54Met). The highest population minor allele frequency in gnomAD v2.1.1 is 0.004092 in the European (non Finnish) population, which is higher than the ClinGen BMEP threshold ([>=0.00185]) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as 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: BA1; -8 points (VCEP specifications version 1; Approved: 1/31/2021) LINK:https://erepo.genome.network/evrepo/ui/classification/CA9306657/MONDO:0100283/018
Frequency
Consequence
NM_005027.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PIK3R2 | NM_005027.4 | c.160G>A | p.Val54Met | missense_variant | Exon 2 of 16 | ENST00000222254.13 | NP_005018.2 | |
PIK3R2 | NR_073517.2 | n.715G>A | non_coding_transcript_exon_variant | Exon 2 of 16 | ||||
PIK3R2 | NR_162071.1 | n.715G>A | non_coding_transcript_exon_variant | Exon 2 of 15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PIK3R2 | ENST00000222254.13 | c.160G>A | p.Val54Met | missense_variant | Exon 2 of 16 | 1 | NM_005027.4 | ENSP00000222254.6 | ||
ENSG00000268173 | ENST00000593731.1 | n.160G>A | non_coding_transcript_exon_variant | Exon 2 of 25 | 2 | ENSP00000471914.1 |
Frequencies
GnomAD3 genomes AF: 0.00231 AC: 351AN: 152246Hom.: 2 Cov.: 32
GnomAD3 exomes AF: 0.00203 AC: 328AN: 161974Hom.: 1 AF XY: 0.00215 AC XY: 190AN XY: 88192
GnomAD4 exome AF: 0.00395 AC: 5559AN: 1408970Hom.: 16 Cov.: 31 AF XY: 0.00384 AC XY: 2673AN XY: 696366
GnomAD4 genome AF: 0.00230 AC: 351AN: 152360Hom.: 2 Cov.: 32 AF XY: 0.00238 AC XY: 177AN XY: 74500
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:3
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PIK3R2: BS2 -
not specified Benign:1
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Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes Benign:1
The c.160G>A (NM_005027.4) variant in PIK3R2 is a missense variant predicted to cause substitution of (p.Val54Met). The highest population minor allele frequency in gnomAD v2.1.1 is 0.004092 in the European (non Finnish) population, which is higher than the ClinGen BMEP threshold ([>=0.00185]) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as 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: BA1; -8 points (VCEP specifications version 1; Approved: 1/31/2021) -
PIK3R2-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at