Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

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Variant: NM_005027.4(PIK3R2):c.322+7A>G

CA9306692

767212 (ClinVar)

Gene: PIK3R2

Condition: overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes

Inheritance Mode: Autosomal dominant inheritance (mosaic)

Link to MONDO

UUID: 279fa48f-a8a8-40f7-9c28-74f2e655e555

HGVS expressions

NM_005027.4:c.322+7A>G

NM_005027.4(PIK3R2):c.322+7A>G

NC_000019.10:g.18156208A>G

CM000681.2:g.18156208A>G

NC_000019.9:g.18267018A>G

CM000681.1:g.18267018A>G

NC_000019.8:g.18128018A>G

NG_033010.1:g.8031A>G

NG_033010.2:g.8031A>G

ENST00000222254.13:c.322+7A>G

ENST00000617130.5:c.322+7A>G

ENST00000617642.2:c.322+7A>G

ENST00000222254.12:c.322+7A>G

ENST00000426902.5:c.322+7A>G

ENST00000593731.1:c.322+7A>G

ENST00000617130.4:n.322+7A>G

ENST00000617642.1:n.322+7A>G

NM_005027.3:c.322+7A>G

NR_073517.1:n.862+7A>G

NR_073517.2:n.877+7A>G

NR_162071.1:n.877+7A>G

Likely Benign

BS1 BP7 BP4

Evidence Links 0

Expert Panel

Brain Malformations VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Brain Malformations VCEP

The c.322+7A>G (NM_005027.4) variant in PIK3R2 is an intronic variant. The highest population minor allele frequency in gnomAD v2.1.1 is 0.0008153 in the Latino/Admixed 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)

BS1

The allele frequency in gnomAD is 0.082% of Latino alleles in gnomAD, which is higher than the BS1 cutoff of 0.037%.

BP7

SpliceAI predicts that this variant does not change splicing. MaxEntScan has similar results.

BP4

No predicted effect on splicing per varSEAK, spliceAI and MaxEntScan.

Approved on: 2022-02-11

Published on: 2022-02-11

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