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_006218.4(PIK3CA):c.2040T>C (p.Val680=)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA2710873

456534 (ClinVar)

Gene: PIK3CA

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

Inheritance Mode: Autosomal dominant inheritance (mosaic)

Link to MONDO

UUID: 090add3d-c9fa-47a7-a15e-fae92822f209

Approved on: 2022-02-11

Published on: 2022-02-11

HGVS expressions

NM_006218.4:c.2040T>C

NM_006218.4(PIK3CA):c.2040T>C (p.Val680=)

NC_000003.12:g.179221010T>C

CM000665.2:g.179221010T>C

NC_000003.11:g.178938798T>C

CM000665.1:g.178938798T>C

NC_000003.10:g.180421492T>C

NG_012113.2:g.77488T>C

ENST00000263967.4:c.2040T>C

ENST00000462255.2:n.502T>C

ENST00000643187.1:c.2040T>C

ENST00000674534.1:n.2948T>C

ENST00000674622.1:n.461T>C

ENST00000675467.1:n.4847T>C

ENST00000675786.1:c.*607T>C

ENST00000263967.3:c.2040T>C

ENST00000462255.1:n.314T>C

NM_006218.2:c.2040T>C

NM_006218.3:c.2040T>C

Likely Benign

BP7 BP4

PM2 BA1 BS1

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 NM_006218.4(PIK3CA): c.2040T>C (p.Val680=) variant is a synonymous (silent) variant that occurs at a nucleotide that is not conserved according to a PhyloP <0.1 (BP7). The results from in silico splicing predictors MaxEntScan, spliceAI and varSEAK support that this variant does not affect splicing (BP4). 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: BP4, BP7; -2 points (VCEP specifications version 1; Approved: 1/31/2021)

BP7

No splicing impact detected by the predictors in Alamut.

BP4

Low phyloP nucleotide conservation score (-1.25) & no predicted splicing impact.

PM2

The frequency in gnomAD is 0.0017% (2/112994) of European alleles.

BA1

The frequency in gnomAD is 0.0017% (2/112994) of European alleles.

BS1

The frequency in gnomAD is 0.0017% (2/112994) of European alleles.

Curation History

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