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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_002524.5(NRAS):c.368G>A (p.Arg123Lys)

CA177518

164809 (ClinVar)

Gene: NRAS
Condition: RASopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 83d5c119-8a88-4482-8ffb-08d114257610
Approved on: 2024-09-17
Published on: 2024-10-31

HGVS expressions

NM_002524.5:c.368G>A
NM_002524.5(NRAS):c.368G>A (p.Arg123Lys)
NC_000001.11:g.114709651C>T
CM000663.2:g.114709651C>T
NC_000001.10:g.115252272C>T
CM000663.1:g.115252272C>T
NC_000001.9:g.115053795C>T
NG_007572.1:g.12244G>A
ENST00000369535.5:c.368G>A
ENST00000369535.4:c.368G>A
NM_002524.4:c.368G>A
More

Uncertain Significance

Met criteria codes 2
PP3 PM2_Supporting
Not Met criteria codes 3
BS1 BP4 BA1

Evidence Links 0

Expert Panel

Criteria Specification Information

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
RASopathy VCEP
The NM_002524.5:c.368G>A variant in NRAS is a missense variant predicted to cause substitution of arginine by lysine at amino acid 123 (p.Arg123Lys). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.759, which is above the threshold of 0.7, evidence that correlates with impact to NRAS function (PP3). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal dominant RASopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy VCEP: PM2_Supporting, PP3. (ClinGen RASopathy VCEP specifications version 2.1; 09/17/2024)
Met criteria codes
PP3
The computational predictor REVEL gives a score of 0.759, which is above the threshold of 0.7, evidence that correlates with impact to NRAS function (PP3).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 (PM2_Supporting).
Not Met criteria codes
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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