NM_005343.4(HRAS):c.546G>A (p.Met182Ile) AND not specified

Germline classification:
Likely benign (1 submission)
Last evaluated:
Feb 19, 2024
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:
RCV003993902.1

Allele description [Variation Report for NM_005343.4(HRAS):c.546G>A (p.Met182Ile)]

NM_005343.4(HRAS):c.546G>A (p.Met182Ile)

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.546G>A (p.Met182Ile)
HGVS:
  • NC_000011.10:g.532660C>T
  • NG_007666.1:g.7891G>A
  • NM_001130442.3:c.546G>A
  • NM_001318054.2:c.309G>A
  • NM_005343.4:c.546G>AMANE SELECT
  • NM_176795.5:c.*115G>A
  • NP_001123914.1:p.Met182Ile
  • NP_001304983.1:p.Met103Ile
  • NP_005334.1:p.Met182Ile
  • LRG_506t1:c.546G>A
  • LRG_506:g.7891G>A
  • LRG_506p1:p.Met182Ile
  • NC_000011.9:g.532660C>T
  • NM_005343.2:c.546G>A
Protein change:
M103I
Links:
dbSNP: rs748639813
NCBI 1000 Genomes Browser:
rs748639813
Molecular consequence:
  • NM_176795.5:c.*115G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001130442.3:c.546G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318054.2:c.309G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005343.4:c.546G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004814067Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely benign
(Feb 19, 2024) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004814067.1

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

Description

Variant summary: HRAS c.546G>A (p.Met182Ile) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.1e-05 in 779530 control chromosomes gnomAD database (v4.0.0). The observed variant frequency is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in HRAS causing Costello Syndrome phenotype (5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.546G>A in individuals affected with Costello Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 240138). Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Apr 20, 2024