NM_033360.4(KRAS):c.15A>T (p.Lys5Asn) AND Noonan syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 3, 2017
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000520745.10

Allele description [Variation Report for NM_033360.4(KRAS):c.15A>T (p.Lys5Asn)]

NM_033360.4(KRAS):c.15A>T (p.Lys5Asn)

Gene:

KRAS:KRAS proto-oncogene, GTPase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p12.1

Genomic location:

Preferred name:

NM_033360.4(KRAS):c.15A>T (p.Lys5Asn)

Other names:

NM_004985.4(KRAS):c.15A>T

HGVS:

NC_000012.12:g.25245370T>A
NG_007524.2:g.10634A>T
NM_001369786.1:c.15A>T
NM_001369787.1:c.15A>T
NM_004985.5:c.15A>TMANE SELECT
NM_033360.4:c.15A>T
NP_001356715.1:p.Lys5Asn
NP_001356716.1:p.Lys5Asn
NP_004976.2:p.Lys5Asn
NP_004976.2:p.Lys5Asn
NP_004976.2:p.Lys5Asn
NP_203524.1:p.Lys5Asn
LRG_344t1:c.15A>T
LRG_344t2:c.15A>T
LRG_344:g.10634A>T
LRG_344p1:p.Lys5Asn
LRG_344p2:p.Lys5Asn
NC_000012.11:g.25398304T>A
NG_007524.1:g.10551A>T
NM_004985.3:c.15A>T
NM_004985.4:c.15A>T
NM_033360.2:c.15A>T
P01116:p.Lys5Asn

Protein change:

K5N; LYS5ASN

Links:

UniProtKB: P01116#VAR_064849; OMIM: 190070.0017; dbSNP: rs104894361

NCBI 1000 Genomes Browser:

rs104894361

Molecular consequence:

NM_001369786.1:c.15A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001369787.1:c.15A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004985.5:c.15A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_033360.4:c.15A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Noonan syndrome (NS)
Synonyms:: Noonan's syndrome; Pseudo-Turner syndrome
Identifiers:: MONDO: MONDO:0018997; MeSH: D009634; MedGen: C0028326; OMIM: PS163950

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000616404	ClinGen RASopathy Variant Curation Expert Panel	reviewed by expert panel (ClinGen RASopathy ACMG Specifications v1)	Pathogenic (Apr 3, 2017)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000616404

ClinGen RASopathy Variant Curation Expert Panel

reviewed by expert panel

(ClinGen RASopathy ACMG Specifications v1)

Pathogenic
(Apr 3, 2017)

germline

curation

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Expansion of the genotypic and phenotypic spectrum in patients with KRAS germline mutations.

Zenker M, Lehmann K, Schulz AL, Barth H, Hansmann D, Koenig R, Korinthenberg R, Kreiss-Nachtsheim M, Meinecke P, Morlot S, Mundlos S, Quante AS, Raskin S, Schnabel D, Wehner LE, Kratz CP, Horn D, Kutsche K.

J Med Genet. 2007 Feb;44(2):131-5. Epub 2006 Oct 20.

PubMed [citation]

PMID:: 17056636
PMCID:: PMC2598066

Details of each submission

From ClinGen RASopathy Variant Curation Expert Panel, SCV000616404.4

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

Description

The c.15A>T (p.Lys5Asn) variant in KRAS has been reported in the literature in at least 2 unconfirmed de novo occurrences in patients with clinical features of a RASopathy (PM6_Strong; GeneDx, Institute of Human Genetics, Otto von Guericke University Magdeburg internal data GTR ID: 26957, 506381 PMID 17056636). The variant has been detected in This variant was absent from large population studies (PM2; ExAC, http://exac.broadinstitute.org). The p.Lys5Asn variant has been identified in at least 4 independent occurrences in patients with a RASopathy (PS4_Moderate; EGL genetics internal data GTR ID: 500060; PMID: 17056636; ClinVar SCV000202928.6). Computational prediction tools and conservation analysis suggest that the p.Lys5Asn variant may impact the protein (PP3). The variant is located in the KRAS gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID: 29493581). In summary, this variant meets criteria to be classified as pathogenic for RASopathies in an autosomal dominant manner. Rasopathy-specific ACMG/AMP criteria applied (PMID:29493581): PM6_Strong, PM2, PS4_Moderate, PP3, PP2)

#	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

Last Updated: Oct 13, 2024

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