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_005343.4(HRAS):c.257A>C (p.Asn86Thr)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA180888

40437 (ClinVar)

Gene: HRAS

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7a67f8eb-da68-4c6b-9d98-ee169176af3c

Approved on: 2024-12-03

Published on: 2025-03-31

HGVS expressions

NM_005343.4:c.257A>C

NM_005343.4(HRAS):c.257A>C (p.Asn86Thr)

NC_000011.10:g.533799T>G

CM000673.2:g.533799T>G

NC_000011.9:g.533799T>G

CM000673.1:g.533799T>G

NC_000011.8:g.523799T>G

NG_007666.1:g.6752A>C

ENST00000397594.7:c.257A>C

ENST00000417302.7:c.257A>C

ENST00000417302.6:c.257A>C

ENST00000462734.2:c.257A>C

ENST00000311189.8:c.257A>C

ENST00000311189.7:c.257A>C

ENST00000397594.5:c.257A>C

ENST00000397596.6:c.257A>C

ENST00000417302.5:c.257A>C

ENST00000451590.5:c.257A>C

ENST00000468682.2:n.745A>C

ENST00000479482.1:n.178A>C

ENST00000493230.5:c.257A>C

NM_001130442.1:c.257A>C

NM_005343.2:c.257A>C

NM_176795.3:c.257A>C

NM_001130442.2:c.257A>C

NM_001318054.1:c.-63A>C

NM_005343.3:c.257A>C

NM_176795.4:c.257A>C

NM_001318054.2:c.-63A>C

NM_001130442.3:c.257A>C

NM_176795.5:c.257A>C

Benign

BP5 BA1

BP4 PP3 PM2 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 HRAS Version 2.3.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.257A>C variant in the HRAS gene is a missense variant predicted to cause substitution of asparagine by threonine at amino acid 86 (p.Asn86Thr). The filtering allele frequency in gnomAD v2.1.1 is 0.0006669 (22/24924 alleles) in the Latino/Admixed American population, which is higher than the ClinGen RASopathy VCEP threshold (>0.0005) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.367, which is neither above nor below the thresholds predicting a damaging or benign impact on HRAS function. This variant has been identified in a patient with an alternate molecular basis for disease (BP5; Partners LMM, GeneDx internal data GTR ID: 21766, 26957, ClinVar SCV000204177.4, SCV000207861.7). In summary, this variant meets criteria to be classified as benign for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: BA1, BP5 (Specification Version 2.3, 12/3/2024)

BP5

This variant has been identified in a patient with an alternate molecular basis for disease (BP5; Partners LMM, GeneDx internal data GTR ID: 21766, 26957, ClinVar SCV000204177.4, SCV000207861.7).

BA1

The filtering allele frequency in gnomAD v2.1.1 is 0.0006669 (22/24924 alleles) in the Latino/Admixed American population, which is higher than the ClinGen RASopathy VCEP threshold (>0.0005) for BA1, and therefore meets this criterion (BA1).

BP4

The computational predictor REVEL gives a score of 0.367, which is neither above nor below the thresholds predicting a damaging or benign impact on HRAS function.

PP3

The computational predictor REVEL gives a score of 0.367, which is neither above nor below the thresholds predicting a damaging or benign impact on HRAS function.

PM2

The filtering allele frequency in gnomAD v2.1.1 is 0.0006669 (22/24924 alleles) in the Latino/Admixed American population, which meets BA1.

BS1

The filtering allele frequency in gnomAD v2.1.1 is 0.0006669 (22/24924 alleles) in the Latino/Admixed American population, which meets BA1.

Curation History

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