Evidence Repository - GenboreeKB

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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Curation History
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CA5779258

830080 (ClinVar)

Gene: HRAS

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d087da2c-a8d8-4831-9a95-aceb4c5528b4

Approved on: 2019-11-04

Published on: 2019-11-04

HGVS expressions

NM_005343.4:c.450+132_450+151del

NC_000011.10:g.533311_533330del

CM000673.2:g.533311_533330del

NC_000011.9:g.533311_533330del

CM000673.1:g.533311_533330del

NC_000011.8:g.523311_523330del

NG_007666.1:g.7230_7249del

ENST00000397594.6:n.206_225del

ENST00000417302.6:c.488_507del

ENST00000462734.2:c.*18_*37del

ENST00000311189.8:c.450+132_450+151del

ENST00000311189.7:c.450+132_450+151del

ENST00000397594.5:c.488_507del

ENST00000397596.6:c.450+132_450+151del

ENST00000417302.5:c.488_507del

ENST00000451590.5:c.450+132_450+151del

ENST00000462734.1:n.181_200del

ENST00000478324.5:n.198_217del

ENST00000479482.1:n.371+132_371+151del

ENST00000493230.5:c.488_507del

NM_001130442.1:c.450+132_450+151del

NM_005343.2:c.450+132_450+151del

NM_176795.3:c.488_507del

NM_001130442.2:c.450+132_450+151del

NM_001318054.1:c.169_188del

NM_005343.3:c.450+132_450+151del

NM_176795.4:c.488_507del

NM_001318054.2:c.169_188del

NM_001130442.3:c.450+132_450+151del

NM_176795.5:c.488_507del

NM_176795.5(HRAS):c.488_507del (p.Leu163fs)

Benign

BA1

PS4 PP3

Evidence Links 1

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.488_507delTCTGGGACCCCCCGGGACCC (p.Leu163HisfsTer30) variant in HRAS is classified as benign because it has been identified in 0.07227% (lower bound of the 95% CI of 21/19470) of East Asian chromosomes in gnomAD (BA1; gnomad.broadinstitute.org). This variant was observed in 1 fetus and 1 older proband with clinical presentations that lacked clear associations with a RASopathy. In summary, this variant meets criteria to be classified as benign. ACMG/AMP Criteria applied: BA1.

BA1

Present in 0.07227% (21/19470) of East Asian chromosomes in gnomAD.

PS4

Fetus not counted towards PS4 because not well-phenotyped Internal data from National Cancer Institute: -1 male patient who had WES to identify a bone marrow failure gene. Initially thought to have a Shwachman-Diamond syndrome-like disease with gastrointestinal problems in addition to pancytopenia. In re-reading of his chart he could fit the Costello phenotype, although he does not have the classic dysmorphology, but some hints of it -Not counted towards PS4 without clear diagnosis

Detected in 1 fetus with a nuchal translucency of 7.2 mm. No additional phenotypes were noted because the pregnancy was terminated at 12 weeks. PubMed:31040167

PP3

Splicing is not predicted to be impacted by Alamut. REVEL score and conservation data not available for deletion.

Curation History

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