Evidence Repository - Clinical Genome Resources

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

Variant: NM_004985.5(KRAS):c.451-14T>C

Curation Version - 1.2
Curation History
JSON LD for Version 1.2

CA176485

138060 (ClinVar)

Gene: KRAS

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8ec28790-8df3-4c37-9e77-84dddf694f7a

Approved on: 2024-09-17

Published on: 2024-10-02

HGVS expressions

NM_004985.5:c.451-14T>C

NM_004985.5(KRAS):c.451-14T>C

NC_000012.12:g.25209925A>G

CM000674.2:g.25209925A>G

NC_000012.11:g.25362859A>G

CM000674.1:g.25362859A>G

NC_000012.10:g.25254126A>G

NG_007524.1:g.45996T>C

NG_007524.2:g.46079T>C

ENST00000557334.6:c.112-14T>C

ENST00000685328.1:c.451-14T>C

ENST00000686877.1:c.*422-14T>C

ENST00000687356.1:c.*149-14T>C

ENST00000688228.1:n.925-14T>C

ENST00000688940.1:c.451-14T>C

ENST00000690406.1:c.254-14T>C

ENST00000690804.1:c.*412-14T>C

ENST00000692768.1:c.253-14T>C

ENST00000693229.1:c.376-14T>C

ENST00000256078.10:c.*5-14T>C

ENST00000311936.8:c.451-14T>C

ENST00000256078.8:c.*5-14T>C

ENST00000311936.7:c.451-14T>C

ENST00000557334.5:c.112-14T>C

NM_004985.4:c.451-14T>C

NM_033360.3:c.*5-14T>C

NM_001369786.1:c.*5-14T>C

NM_001369787.1:c.451-14T>C

NM_033360.4:c.*5-14T>C

Likely Benign

BP7 BP4

PP3 PM2 BA1 BS1

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specification: ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for KRAS Version 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.451-14T>C variant in the KRAS gene is an intronic variant located in intron 6. The filtering allele frequency in gnomAD v4.1.0 is 0.01135% (10/73838 alleles) in the African/African American population (PM2_Supporting/ BS1/ BA1 are not met).This variant is located at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP4, BP7). In summary, this variant meets criteria to be classified as likely benign for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: BP4, BP7 (Specification Version 2.1, 09/17/2024)

BP7

The c.451-14T>C variant is an intronic variant at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP7).

BP4

Computational prediction tools and conservation analysis suggest that the variant does not impact the splice consensus sequence nor the creation of a new splice site (BP4).

PP3

Computational prediction tools and conservation analysis suggest that the variant does not impact the protein (BP4).

PM2

The filtering allele frequency in gnomAD v4.1.0 is 0.01135% (10/73838 alleles) in the African/African American population (PM2_Supporting/BS1/BA1 are not met).

BA1

The filtering allele frequency in gnomAD v4.1.0 is 0.01135% (10/73838 alleles) in the African/African American population (PM2_Supporting/BS1/BA1 are not met).

BS1

The filtering allele frequency in gnomAD v4.1.0 is 0.01135% (10/73838 alleles) in the African/African American population (PM2_Supporting/BS1/BA1 are not met).

Curation History

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