Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • See Evidence submitted by expert panel for details.

Variant: NM_004985.4(KRAS):c.15A>T (p.Lys5Asn)

CA234191

12594 (ClinVar)

Gene: KRAS
Condition: Noonan syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 15c2f120-e3bd-4bf0-8ecb-86290c93de7c
Approved on: 2020-05-18
Published on: 2020-07-01

HGVS expressions

NM_004985.4:c.15A>T
NM_004985.4(KRAS):c.15A>T (p.Lys5Asn)
NM_033360.3:c.15A>T
NM_001369786.1:c.15A>T
NM_001369787.1:c.15A>T
NM_004985.5:c.15A>T
NM_033360.4:c.15A>T
ENST00000256078.8:c.15A>T
ENST00000311936.7:c.15A>T
ENST00000556131.1:c.15A>T
ENST00000557334.5:c.15A>T
NC_000012.12:g.25245370T>A
CM000674.2:g.25245370T>A
NC_000012.11:g.25398304T>A
CM000674.1:g.25398304T>A
NC_000012.10:g.25289571T>A
NG_007524.1:g.10551A>T
NG_007524.2:g.10634A>T
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Pathogenic

Met criteria codes 5
PM2 PP3 PP2 PS4_Moderate PM6_Strong

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
RASopathy VCEP
The c.15A>T (p.Lys5Asn) variant in KRAS has been reported in at least 2 unconfirmed de novo occurrences in patients with clinical features of a RASopathy (PM6_Strong; PMID: 17056636, GeneDx internal data). This variant was absent from large population studies (PM2; gnomad.broadinstitute.org). The p.Lys5Asn variant has been identified in at least 4 independent occurrences in patients with a RASopathy (PS4_Moderate; PMID: 17056636, GeneDx, EGL Genetics internal data, ClinVar SCV000202928.7). Computational prediction tools and conservation analysis suggest that the p.Lys5Asn variant may impact protein function (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): PS4_Moderate, PM6_Strong, PM2, PP2, PP3.
Met criteria codes
PM2
Absent from both versions of gnomAD.
PP3
Computational prediction tools and conservation analysis suggest that the p.Lys5Asn variant may impact the protein (PP3).
PP2
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).
PS4_Moderate
The p.Lys5Asn variant has been identified in at least 4 independent occurrences in patients with a RASopathy (PS4_Moderate; PMID: 17056636, GeneDx, EGL Genetics internal data, ClinVar SCV000202928.7).
Cases PubMed:17056636
PM6_Strong
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; PMID: 17056636, GeneDx internal data).
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, Zenker et al. internal data PMID 17056636). PubMed:17056636
Curation History
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