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_002709.3(PPP1CB):c.201A>G (p.Gln67=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA1589199

667025 (ClinVar)

Gene: PPP1CB

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 92c34e06-f193-405c-a099-e2ab6cede4d0

Approved on: 2024-12-03

Published on: 2025-03-25

HGVS expressions

NM_002709.3:c.201A>G

NM_002709.3(PPP1CB):c.201A>G (p.Gln67=)

NC_000002.12:g.28778825A>G

CM000664.2:g.28778825A>G

NC_000002.11:g.29001691A>G

CM000664.1:g.29001691A>G

NC_000002.10:g.28855195A>G

NG_052878.1:g.32078A>G

ENST00000418910.2:c.201A>G

ENST00000420282.6:c.201A>G

ENST00000427786.2:c.*161A>G

ENST00000441461.6:c.201A>G

ENST00000455580.6:c.117A>G

ENST00000703171.1:c.*248A>G

ENST00000703172.1:c.117A>G

ENST00000703173.1:c.201A>G

ENST00000703174.1:c.201A>G

ENST00000703176.1:c.168A>G

ENST00000703177.1:c.*161A>G

ENST00000395366.3:c.201A>G

ENST00000296122.10:c.201A>G

ENST00000358506.6:c.201A>G

ENST00000395366.2:c.201A>G

ENST00000420282.5:c.201A>G

ENST00000427786.1:c.*161A>G

ENST00000441461.5:c.201A>G

ENST00000455580.5:c.117A>G

NM_002709.2:c.201A>G

NM_206876.1:c.201A>G

NM_206876.2:c.201A>G

Benign

BA1 BP7 BP4

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specification: ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PPP1CB Version 1.3.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.201A>G (p.Gln67=) variant in PPP1CB is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing. In addition, the computational predictor REVEL does not predict a damaging effect on PPP1CB function (BP4, BP7). The filtering allele frequency in gnomAD v2 is 60.64% in the European (non-Finnish) population, which is higher than the ClinGen RASopathy VCEP threshold (>0.0005) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for autosomal dominant RASopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy VCEP: BA1, BP4, BP7. (RASopathy VCEP specifications version 1.3; 12/3/2024)

BA1

The highest population minor allele frequency in gnomAD v4 is 62.67% (3738/5964) in the Middle Eastern population, which is higher than the ClinGen RASopathy VCEP threshold (>0.0005) for BA1

BP7

The variant is not predicted by SpliceAI to impact splicing

BP4

The computational predictor REVEL does not predict a damaging effect on PPP1CB function

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.