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: MAP2K2 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_030662.4(MAP2K2):c.844C>T (p.Pro282Ser)

CA137972

40826 (ClinVar)

Gene: MAP2K2
Condition: RASopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 413325d3-6867-4b66-a6a6-655f337675bc
Approved on: 2024-12-03
Published on: 2025-03-31

HGVS expressions

NM_030662.4:c.844C>T
NM_030662.4(MAP2K2):c.844C>T (p.Pro282Ser)
NC_000019.10:g.4099276G>A
CM000681.2:g.4099276G>A
NC_000019.9:g.4099274G>A
CM000681.1:g.4099274G>A
NC_000019.8:g.4050274G>A
NG_007996.1:g.29853C>T
ENST00000394867.9:n.1283C>T
ENST00000687128.1:n.1283C>T
ENST00000688002.1:n.1138C>T
ENST00000689792.1:n.748C>T
ENST00000262948.10:c.844C>T
ENST00000262948.9:c.844C>T
ENST00000394867.8:c.553C>T
ENST00000593364.5:n.791C>T
ENST00000595715.1:n.659C>T
ENST00000597263.5:n.169+1743C>T
ENST00000599021.1:c.29+1743C>T
ENST00000600584.5:n.1404C>T
ENST00000601786.5:n.1145C>T
NM_030662.3:c.844C>T
More

Benign

Met criteria codes 3
BP5 BP4 BA1
Not Met criteria codes 3
BS1 PP3 PM2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MAP2K2 Version 2.3.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
RASopathy VCEP
The c.844C>T variant in the MAP2K2 gene is a missense variant predicted to cause substitution of proline by serine at amino acid 282 (p.Pro282Ser). The filtering allele frequency in gnomAD v2.1.1 is 0.001415 (42/22756 alleles) in the African/African American population, meeting the criterion for BA1. The computational predictor REVEL gives a score of 0.072, which predicts no impact on protein function (BP4). This variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx internal data; GTR ID's 26957; SCV000207963.8). 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, BP4, BP5 (Specification Version 2.3, 12/3/2024)
Met criteria codes
BP5
This variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx internal data; GTR ID's 26957; SCV000207963.8).
BP4
The computational predictor REVEL gives a score of 0.072, which predicts no impact on protein function
BA1
The filtering allele frequency in gnomAD v2.1.1 is 0.001415 (42/22756 alleles) in the African/African American population, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1).
Not Met criteria codes
BS1
The filtering allele frequency in gnomAD v2.1.1 is 0.001415 (42/22756 alleles) in the African/African American population, meeting BA1
PP3
The computational predictor REVEL gives a score of 0.072, which predicts no impact on protein function
PM2
The filtering allele frequency in gnomAD v2.1.1 is 0.001415 (42/22756 alleles) in the African/African American population, meeting BA1
Curation History
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