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]

Variant: NM_005027.4(PIK3R2):c.160G>A (p.Val54Met)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA9306657

468317 (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: 01200966-ff55-4274-8597-25b027b3187e

Approved on: 2022-02-11

Published on: 2022-02-11

HGVS expressions

NM_005027.4:c.160G>A

NM_005027.4(PIK3R2):c.160G>A (p.Val54Met)

NC_000019.10:g.18156039G>A

CM000681.2:g.18156039G>A

NC_000019.9:g.18266849G>A

CM000681.1:g.18266849G>A

NC_000019.8:g.18127849G>A

NG_033010.1:g.7862G>A

NG_033010.2:g.7862G>A

ENST00000222254.13:c.160G>A

ENST00000617130.5:c.160G>A

ENST00000617642.2:c.160G>A

ENST00000222254.12:c.160G>A

ENST00000426902.5:c.160G>A

ENST00000593731.1:c.160G>A

ENST00000617130.4:n.160G>A

ENST00000617642.1:n.160G>A

NM_005027.3:c.160G>A

NR_073517.1:n.700G>A

NR_073517.2:n.715G>A

NR_162071.1:n.715G>A

Benign

BA1

PP2

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.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)

BA1

The frequency in gnomAD is 0.409% of European alleles, including 1 homozygous observation, which exceeds the BA1 cutoff of 0.185%.

PP2

The missense Z score is 2.33 in gnomAD, which is lower than the 3.09 cutoff.

Curation History

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