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 label mismatch: NRAS vs undefined
  • 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.159G>A (p.Leu53=)

CA177515

164807 (ClinVar)

Gene: NRAS
Condition: RASopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 6db104c5-3d96-463b-8fb7-7ff42dc61863
Approved on: 2024-12-03
Published on: 2025-03-26

HGVS expressions

NM_002524.5:c.159G>A
NM_002524.5(NRAS):c.159G>A (p.Leu53=)
NC_000001.11:g.114713931C>T
CM000663.2:g.114713931C>T
NC_000001.10:g.115256552C>T
CM000663.1:g.115256552C>T
NC_000001.9:g.115058075C>T
NG_007572.1:g.7964G>A
ENST00000369535.5:c.159G>A
ENST00000369535.4:c.159G>A
NM_002524.4:c.159G>A
More

Benign

Met criteria codes 1
BA1
Not Met criteria codes 2
BP7 PM1

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 2.3.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
RASopathy VCEP
The NM_002524.5:c.159G>A variant is a synonymous (silent) variant (p.Leu53=) that is not predicted by SpliceAI to impact splicing, however, this nucleotide is highly conserved. The filtering allele frequency (the lower threshold of the 95% CI of 25/19928) of the c.159G>A variant in NRAS is 0.0009003 for East Asian chromosomes by gnomAD v2.1.1, which is higher than the ClinGen RASopathy VCEP threshold (≥0.0005) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for autosomal dominant RASopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy VCEP: BA1. (ClinGen RASopathy VCEP specifications version 2.3; 12/3/2024)
Met criteria codes
BA1
Present in 0.1255% (25/19,928) of East Asian alleles in gnomAD v2 (95% CI 0.08722%). Present in 0.06300% (3/4,762) of East Asian alleles in gnomAD v3.
Not Met criteria codes
BP7
PhastCons and phyloP indicate that this nucleotide is highly conserved.
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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