NM_005343.4(HRAS):c.506G>A (p.Arg169Gln) AND Costello syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 14, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000463046.10

Allele description [Variation Report for NM_005343.4(HRAS):c.506G>A (p.Arg169Gln)]

NM_005343.4(HRAS):c.506G>A (p.Arg169Gln)

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.506G>A (p.Arg169Gln)

HGVS:

NC_000011.10:g.532700C>T
NG_007666.1:g.7851G>A
NM_001130442.3:c.506G>A
NM_001318054.2:c.269G>A
NM_005343.4:c.506G>AMANE SELECT
NM_176795.5:c.*75G>A
NP_001123914.1:p.Arg169Gln
NP_001304983.1:p.Arg90Gln
NP_005334.1:p.Arg169Gln
LRG_506t1:c.506G>A
LRG_506:g.7851G>A
LRG_506p1:p.Arg169Gln
NC_000011.9:g.532700C>T
NM_005343.2:c.506G>A
NM_005343.3:c.506G>A

Protein change:

R169Q

Links:

dbSNP: rs142218590

NCBI 1000 Genomes Browser:

rs142218590

Molecular consequence:

NM_176795.5:c.*75G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001130442.3:c.506G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318054.2:c.269G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005343.4:c.506G>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000550344	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25742471, 28492532
SCV001481324	Baylor Genetics - CSER-TexasKidsCanSeq	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 31, 2019)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000550344

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 14, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001481324

Baylor Genetics - CSER-TexasKidsCanSeq

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 31, 2019)

maternal

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Assessing the clinical value of targeted massively parallel sequencing in a longitudinal, prospective population-based study of cancer patients.

Wong SQ, Fellowes A, Doig K, Ellul J, Bosma TJ, Irwin D, Vedururu R, Tan AY, Weiss J, Chan KS, Lucas M, Thomas DM, Dobrovic A, Parisot JP, Fox SB.

Br J Cancer. 2015 Apr 14;112(8):1411-20. doi: 10.1038/bjc.2015.80. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25742471
PMCID:: PMC4402458

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000550344.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 169 of the HRAS protein (p.Arg169Gln). This variant is present in population databases (rs142218590, gnomAD 0.01%). This missense change has been observed in individual(s) with an unspecified cancer (PMID: 25742471). ClinVar contains an entry for this variant (Variation ID: 180856). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt HRAS function. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics - CSER-TexasKidsCanSeq, SCV001481324.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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