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NM_005343.4(HRAS):c.179_205dup (p.Arg68_Asp69insGlyGlnGluGluTyrSerAlaMetArg) AND HRAS-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 20, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003400256.5

Allele description [Variation Report for NM_005343.4(HRAS):c.179_205dup (p.Arg68_Asp69insGlyGlnGluGluTyrSerAlaMetArg)]

NM_005343.4(HRAS):c.179_205dup (p.Arg68_Asp69insGlyGlnGluGluTyrSerAlaMetArg)

Genes:
HRAS:HRas proto-oncogene, GTPase [Gene - OMIM - HGNC]
LRRC56:leucine rich repeat containing 56 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
11p15.5
Genomic location:
Preferred name:
NM_005343.4(HRAS):c.179_205dup (p.Arg68_Asp69insGlyGlnGluGluTyrSerAlaMetArg)
HGVS:
  • NC_000011.10:g.533852_533878dup
  • NG_007666.1:g.6674_6700dup
  • NG_121454.1:g.161_187dup
  • NG_121454.2:g.161_187dup
  • NM_001130442.3:c.179_205dup
  • NM_001318054.2:c.-141_-115dup
  • NM_005343.4:c.179_205dupMANE SELECT
  • NM_176795.5:c.179_205dup
  • NP_001123914.1:p.Arg68_Asp69insGlyGlnGluGluTyrSerAlaMetArg
  • NP_005334.1:p.Arg68_Asp69insGlyGlnGluGluTyrSerAlaMetArg
  • NP_789765.1:p.Arg68_Asp69insGlyGlnGluGluTyrSerAlaMetArg
  • LRG_506t1:c.179_205dup
  • LRG_506:g.6674_6700dup
  • LRG_506p1:p.Arg68_Asp69insGlyGlnGluGluTyrSerAlaMetArg
  • NC_000011.9:g.533852_533878dup
  • NM_005343.3:c.179_205dup27
Molecular consequence:
  • NM_001318054.2:c.-141_-115dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001130442.3:c.179_205dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_005343.4:c.179_205dup - inframe_insertion - [Sequence Ontology: SO:0001821]
  • NM_176795.5:c.179_205dup - inframe_insertion - [Sequence Ontology: SO:0001821]

Condition(s)

Name:
HRAS-related disorder
Synonyms:
HRAS-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004103212PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Likely pathogenic
(May 20, 2024) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004103212.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The HRAS c.179_205dup27 variant is predicted to result in an in-frame duplication (p.Gly60_Arg68dup). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Of note, this variant has been reported de novo at PreventionGenetics in a fetal demise with features suspect of Noonan syndrome, including cystic hygroma, pleural effusion, pelviectasis, and possibly congenital heart disease (Internal Data). Similar inframe duplications (p.Glu62_Arg68dup, p.Glu63_Asp69dup) have been reported in individuals with Costello syndrome with functional studies supporting their pathogenicity (Nagai et al. 2022. PubMed ID: 34618388). Additionally, this duplication overlaps multiple pathogenic missense variants (p.Gly60Asp, p.Gly60Val, p.Glu63Lys) reported in individuals with HRAS-related disease (Gripp et al. 2015. PubMed ID: 25914166; Gripp et al. 2017. PubMed ID: 28139825; van der Burgt et al. 2007. PubMed ID: 17412879). Taken together, this variant is interpreted as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024