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]

Link to SEPIO compliant JSON-LD document

CA296087

180859 (ClinVar)

Gene: KRAS

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 77516727-ce20-4572-a118-1fa6f09a2a32

Approved on: 2019-09-24

Published on: 2019-10-02

HGVS expressions

NC_000012.12:g.25209854T>A

CM000674.2:g.25209854T>A

NC_000012.11:g.25362788T>A

CM000674.1:g.25362788T>A

NC_000012.10:g.25254055T>A

NG_007524.1:g.46067A>T

NM_004985.4:c.508A>T

NM_033360.3:c.*62A>T

ENST00000256078.8:c.*62A>T

ENST00000311936.7:c.508A>T

ENST00000557334.5:c.169A>T

Uncertain Significance

PP2 PM2

PS4 PM1

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.508A>T (p.Met170Leu) variant in KRAS was absent from large population studies (PM2; https://gnomad.broadinstitute.org). It was reported in 1 individual with a presentation that lacked a clear association with a RASopathy (PS4 not applied; SCV000310757.1) Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. This variant is located in the KRAS gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants, and pathogenic missense variants are common (PP2; PMID: 29493581). In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PP2.

PP2

KRAS is a missense-constrained gene.

PM2

Absent from gnomAD with high coverage.

PS4

Observed in 1 Irish/German/Bolivian/Czech/Jewish individual, 6 years old at time of testing, presenting with ptosis and pectus excavatum (PreventionGenetics internal data; SCV000310757.1). However, this information is not specific enough to apply PS4.

PM1

Does not occur at G12, G13, V14, T58, A59, G60, Q61, E62, or E63.

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.