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]

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Variant: NM_030662.4(MAP2K2):c.784G>A (p.Val262Ile)

CA137966

46242 (ClinVar)

Gene: MAP2K2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 89d53e74-33f3-465b-abde-d4f656802fed

Approved on: 2024-01-02

Published on: 2024-09-27

HGVS expressions

NM_030662.4:c.784G>A

NM_030662.4(MAP2K2):c.784G>A (p.Val262Ile)

NC_000019.10:g.4099336C>T

CM000681.2:g.4099336C>T

NC_000019.9:g.4099334C>T

CM000681.1:g.4099334C>T

NC_000019.8:g.4050334C>T

NG_007996.1:g.29793G>A

ENST00000394867.9:n.1223G>A

ENST00000687128.1:n.1223G>A

ENST00000688002.1:n.1078G>A

ENST00000689792.1:n.688G>A

ENST00000262948.10:c.784G>A

ENST00000262948.9:c.784G>A

ENST00000394867.8:c.493G>A

ENST00000593364.5:n.731G>A

ENST00000595715.1:n.599G>A

ENST00000597263.5:n.169+1683G>A

ENST00000599021.1:c.29+1683G>A

ENST00000600584.5:n.1344G>A

ENST00000601786.5:n.1085G>A

NM_030662.3:c.784G>A

Uncertain Significance

BP4

BS1 PS4 PP3 PM2 BA1

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 MAP2K2 Version 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.784G>A variant in the MAP2K2 gene is a missense variant predicted to cause substitution of valine by isoleucine at amino acid 262 (p.Val262Ile). The filtering allele frequency in gnomAD v4.1.0 is 0.01543% (201/1178752 alleles) in the European (non-Finnish) population (PM2_Supporting/BS1/BA1 are not met). The computational predictor REVEL gives a score of 0.219, which predicts no impact on protein function (BP4). This variant has been identified in 4 independent occurrences in patients with disparate phenotypes of RASopathy (PS4 not met; GeneDx, LMM internal data; GTR ID's 26957, 21766; SCV000207950.9, SCV000063182.5). In summary, this variant meets criteria to be classified as variant of uncertain significance for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: BP4 (Specification Version 2, 1/2/2024)

BP4

REVEL gives a score of 0.219, which predicts no impact on protein function (BP4).

BS1

The filtering allele frequency in gnomAD v4.1.0 is 0.01543% (201/1178752 alleles) in the European (non-Finnish) population (PM2_Supporting/BS1/BA1 are not met).

PS4

Identified in 4 independent occurrences in patients with disparate phenotypes (PS4 not met; GeneDx, Laboratory for Molecular Medicine internal data; ClinVar SCV000207950.9; SCV000063182.5).

PP3

REVEL gives a score of 0.219, which predicts no impact on protein function (BP4).

PM2

The filtering allele frequency in gnomAD v4.1.0 is 0.01543% (201/1178752 alleles) in the European (non-Finnish) population (PM2_Supporting/BS1/BA1 are not met).

BA1

The filtering allele frequency in gnomAD v4.1.0 is 0.01543% (201/1178752 alleles) in the European (non-Finnish) population (PM2_Supporting/BS1/BA1 are not met).

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