Variant: NM_002524.5(NRAS):c.553C>T (p.Pro185Ser)

CA183538

179025 (ClinVar)

Gene: NRAS

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

UUID: 46bd244c-2ac0-4b2b-b668-0c0991916630

Approved on: 2024-12-03

Published on: 2025-03-26

HGVS expressions

NM_002524.5:c.553C>T
NM_002524.5(NRAS):c.553C>T (p.Pro185Ser)
NC_000001.11:g.114708552G>A
CM000663.2:g.114708552G>A
NC_000001.10:g.115251173G>A
CM000663.1:g.115251173G>A
NC_000001.9:g.115052696G>A
NG_007572.1:g.13343C>T
ENST00000369535.5:c.553C>T
ENST00000369535.4:c.553C>T
NM_002524.4:c.553C>T

Uncertain Significance

• Met criteria codes: BP4

• Not Met criteria codes: PP3 PM2 BA1 BS1

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specification: ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for NRAS Version 2.3.0

Evidence submitted by expert panel

RASopathy VCEP

The NM_002524.5:c.553C>T variant in NRAS is a missense variant predicted to cause substitution of proline by serine at amino acid 185 (p.Pro185Ser). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006663 (14/129152 alleles) in the European (non-Finnish) population (Optional: PM2_Supporting, BS1, and BA1 are not met). The computational predictor REVEL gives a score of 0.051, which is below the threshold of 0.3, evidence that does not predict a damaging effect on NRAS function (BP4). 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: BP4 (ClinGen RASopathy VCEP specifications version 2.3; 12/3/2024)

Met criteria codes

• BP4: The computational predictor REVEL gives a score of 0.051, which is below the threshold of 0.3, evidence that does not predict a damaging effect on NRAS function (BP4).

Not Met criteria codes

• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• PM2: The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006663 (14/129152 alleles) in the European (non-Finnish) population (Optional: PM2_Supporting, BS1, and BA1 are not met).
• BA1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline