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

Variant: NM_176795.4(HRAS):c.277A>G (p.Ile93Val)

CA296061

40439 (ClinVar)

Gene: HRAS

Condition: Costello syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: f12837d2-3463-4374-982c-98e2b63c406a

HGVS expressions

NM_176795.4:c.277A>G

NM_176795.4(HRAS):c.277A>G (p.Ile93Val)

NC_000011.10:g.533779T>C

CM000673.2:g.533779T>C

NC_000011.9:g.533779T>C

CM000673.1:g.533779T>C

NC_000011.8:g.523779T>C

NG_007666.1:g.6772A>G

NM_001130442.1:c.277A>G

NM_005343.2:c.277A>G

NM_176795.3:c.277A>G

NM_001130442.2:c.277A>G

NM_001318054.1:c.-43A>G

NM_005343.3:c.277A>G

NM_005343.4:c.277A>G

NM_001318054.2:c.-43A>G

ENST00000311189.7:c.277A>G

ENST00000397594.5:c.277A>G

ENST00000397596.6:c.277A>G

ENST00000417302.5:c.277A>G

ENST00000451590.5:c.277A>G

ENST00000479482.1:n.198A>G

ENST00000493230.5:c.277A>G

Uncertain Significance

PP2 BP4

PS4 BS2 PM2

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.277A>G (p.Ile93Val) variant has been identified in at least 1 proband with features of a RASopathy, but no clinical diagnosis (PS4_Supporting not met; GeneDx internal data; ClinVar SCV000207855.10). An additional proband inherited this variant from an asymptomatic parent (BS2 not met; Blueprint Genetics internal data, ClinVar SCV000188770.2). The p.Ile93Val variant was present in 0.00398% (1/25120) of Finnish alleles in gnomAD (PM2 not met). Computational prediction tools and conservation analysis suggest that the p.Ile93Val variant does not impact the protein (BP4). The variant is located in the HRAS 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 the p.Ile93Val variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): PP2, BP4

PP2

The variant is located in the HRAS 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).

BP4

Computational prediction tools and conservation analysis suggest that the p.Ile93Val variant does not impact the protein (BP4).

PS4

BS2

An additional proband inherited this variant from an asymptomatic parent (BS2 not met; Blueprint Genetics internal data, ClinVar SCV000188770.2).

PM2

Present in 0.00398% (1/25120) of Finnish alleles in gnomAD (PM2 not met).

Approved on: 2020-07-01

Published on: 2020-07-01

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.