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_030662.3(MAP2K2):c.169T>G (p.Phe57Val)

CA279960

8273 (ClinVar)

Gene: MAP2K2

Condition: cardiofaciocutaneous syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ac054f0f-9da0-455d-8a0f-343d2f4ad540

Approved on: 2017-05-09

Published on: 2019-07-15

HGVS expressions

NM_030662.3:c.169T>G

NM_030662.3(MAP2K2):c.169T>G (p.Phe57Val)

NC_000019.10:g.4117553A>C

CM000681.2:g.4117553A>C

NC_000019.9:g.4117551A>C

CM000681.1:g.4117551A>C

NC_000019.8:g.4068551A>C

NG_007996.1:g.11576T>G

ENST00000262948.9:c.169T>G

ENST00000394867.8:c.-123T>G

ENST00000599345.1:n.366T>G

Pathogenic

PS2_Very Strong PP2 PP3 PM2 PM1

Evidence Links 1

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.169T>G (p.Phe57Val) variant in MAP2K2 has been reported as a confirmed de novo occurrence in at least 2 patients with clinical features of a RASopathy (PS2_VeryStrong; PMID 18042262). The variant is in a location that has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot or domain of MAP2K2 (PM1; PMID 29493581). This variant was absent from large population studies (PM2; ExAC, http://exac.broadinstitute.org). The variant is located in the MAP2K2 gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID: 29493581). Computational prediction tools and conservation analysis suggest that the p.Phe57Val variant may impact the protein (PP3). In summary, this variant meets criteria to be classified as pathogenic for RASopathies in an autosomal dominant manner. Rasopathy-specific ACMG/AMP criteria applied (PMID:29493581): PS2_VeryStrong, PM1, PM2, PP2, PP3.

PS2_Very Strong

The c.169T>G (p.Phe57Val) variant in MAP2K2 has been reported as a confirmed de novo occurrence in at least 2 patients with clinical features of a RASopathy (PS2_VeryStrong; PMID 18042262).

2 patients were identified with confirmed de novo occurrences of the p.Phe57Val PubMed:18042262

PP2

The variant is located in the MAP2K2 gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic missense variants are common (PP2; PMID: 29493581).

PP3

Computational prediction tools and conservation analysis suggest that the p.Phe57Val variant may impact the protein (PP3).

PM2

This variant was absent from large population studies (PM2; ExAC, http://exac.broadinstitute.org).

PM1

The variant is in a location that has been defined by the ClinGen RASopathy Expert Panel to be a mutational hotspot or domain of MAP2K2 (PM1; PMID 29493581).

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