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
PM1 PM2 PS4_Supporting PP2

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
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
PP2
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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