Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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  • See Evidence submitted by expert panel for details.

CA1139533052

Gene: HRAS
Condition: RASopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: c2479285-9bff-473b-8e39-944a6f1c7c54

HGVS expressions

NM_001318054.2:c.-145_-144delinsTT
NM_001130442.1:c.175_176delinsTT
NM_005343.2:c.175_176delinsTT
NM_176795.3:c.175_176delinsTT
NM_001130442.2:c.175_176delinsTT
NM_001318054.1:c.-145_-144delinsTT
NM_005343.3:c.175_176delinsTT
NM_176795.4:c.175_176delinsTT
NM_005343.4:c.175_176delinsTT
NM_001130442.3:c.175_176delinsTT
NM_176795.5:c.175_176delinsTT
ENST00000311189.7:c.175_176delinsTT
ENST00000397594.5:c.175_176delinsTT
ENST00000397596.6:c.175_176delinsTT
ENST00000417302.5:c.175_176delinsTT
ENST00000451590.5:c.175_176delinsTT
ENST00000468682.2:n.663_664delinsTT
ENST00000479482.1:n.96_97delinsTT
ENST00000493230.5:c.175_176delinsTT
NC_000011.10:g.533880_533881delinsAA
CM000673.2:g.533880_533881delinsAA
NC_000011.9:g.533880_533881delinsAA
CM000673.1:g.533880_533881delinsAA
NC_000011.8:g.523880_523881delinsAA
NG_007666.1:g.6670_6671delinsTT

Likely Pathogenic

Met criteria codes 4
PP2 PM1 PM2 PS4_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
RASopathy VCEP
The c.175_176delinsTT (p.Ala59Phe) in HRAS was absent from gnomAD (PM2; PMID: 29493581). It has been identified in one individual with clinical features of a RASopathy (PS4_Supporting; Otto-von-Guericke University Magdeburg internal data). Furthermore, this variant is in a location that has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot of HRAS (PM1; PMID 29493581). 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 c.175_176delinsTT (p.Ala59Phe) variant is likely pathogenic. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): PP2, PM1, PM2, PS4_Supporting.
Met criteria codes
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Defined hotspots for HRAS: HRAS G12, G13, V14, T58, A59, G60, Q61, E62, E63
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4_Supporting
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2021-01-11
Published on: 2021-01-11
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