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_030662.3(MAP2K2):c.619G>A (p.Glu207Lys)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA180944

40813 (ClinVar)

Gene: MAP2K2

Condition: cardiofaciocutaneous syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 93491eab-4df5-480a-a62b-7022611f18ee

Approved on: 2020-06-25

Published on: 2020-06-25

HGVS expressions

NM_030662.3:c.619G>A

NM_030662.3(MAP2K2):c.619G>A (p.Glu207Lys)

NM_030662.4:c.619G>A

ENST00000262948.9:c.619G>A

ENST00000394867.8:c.328G>A

ENST00000593364.5:n.566G>A

ENST00000597008.5:n.220G>A

ENST00000597263.5:n.83G>A

ENST00000599345.1:n.889G>A

ENST00000601786.5:n.920G>A

ENST00000602167.5:n.339G>A

NC_000019.10:g.4101105C>T

CM000681.2:g.4101105C>T

NC_000019.9:g.4101103C>T

CM000681.1:g.4101103C>T

NC_000019.8:g.4052103C>T

NG_007996.1:g.28024G>A

Pathogenic

PM6 PM2 PS2 PS4 PP2

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.619G>A (p.Glu207Lys) variant in MAP2K2 was absent from large population studies (PM2; gnomAD.broadinstitute.org). It has been identified in 6 individuals with clinical features of a RASopathy (PS4; SCV000204213.4, SCV000207959.10, SCV000815593.1, Otto von Guericke University Magdeburg internal data). One of these cases was a confirmed de novo occurrence and another was an unconfirmed de novo occurrence (PS2; PM6; SCV000815593.1, Otto von Guericke University Magdeburg internal data). Additionally, the c.619G>A (p.Glu207Lys) is located in MAP2K2, 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). 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): PS4, PS2, PM6, PM2, PP2.

PM6

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PS4

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

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).

Curation History

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