U.S. flag

An official website of the United States government

NM_005343.4(HRAS):c.452G>C (p.Gly151Ala) AND Costello syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 23, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000525978.6

Allele description [Variation Report for NM_005343.4(HRAS):c.452G>C (p.Gly151Ala)]

NM_005343.4(HRAS):c.452G>C (p.Gly151Ala)

Genes:
HRAS:HRas proto-oncogene, GTPase [Gene - OMIM - HGNC]
LRRC56:leucine rich repeat containing 56 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.5
Genomic location:
Preferred name:
NM_005343.4(HRAS):c.452G>C (p.Gly151Ala)
HGVS:
  • NC_000011.10:g.532754C>G
  • NG_007666.1:g.7797G>C
  • NM_001130442.3:c.452G>C
  • NM_001318054.2:c.215G>C
  • NM_005343.4:c.452G>CMANE SELECT
  • NM_176795.5:c.*21G>C
  • NP_001123914.1:p.Gly151Ala
  • NP_001304983.1:p.Gly72Ala
  • NP_005334.1:p.Gly151Ala
  • LRG_506t1:c.452G>C
  • LRG_506:g.7797G>C
  • LRG_506p1:p.Gly151Ala
  • NC_000011.9:g.532754C>G
  • NM_005343.2:c.452G>C
Protein change:
G151A
Links:
dbSNP: rs1362209698
NCBI 1000 Genomes Browser:
rs1362209698
Molecular consequence:
  • NM_176795.5:c.*21G>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001130442.3:c.452G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318054.2:c.215G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005343.4:c.452G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Costello syndrome (CSTLO)
Synonyms:
FACIOCUTANEOSKELETAL SYNDROME; FCS SYNDROME
Identifiers:
MONDO: MONDO:0009026; MedGen: C0587248; Orphanet: 3071; OMIM: 218040

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000635090Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 23, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000635090.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 151 of the HRAS protein (p.Gly151Ala). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 462154). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Jan 13, 2025