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.1187C>T (p.Thr396Met)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA9090685

279960 (ClinVar)

Gene: MAP2K2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 32490451-6514-4213-8812-6ac300cb461e

Approved on: 2019-12-05

Published on: 2019-12-05

HGVS expressions

NM_030662.3:c.1187C>T

NM_030662.3(MAP2K2):c.1187C>T (p.Thr396Met)

NC_000019.10:g.4090614G>A

CM000681.2:g.4090614G>A

NC_000019.9:g.4090612G>A

CM000681.1:g.4090612G>A

NC_000019.8:g.4041612G>A

NG_007996.1:g.38515C>T

ENST00000262948.9:c.1187C>T

ENST00000394867.8:c.896C>T

ENST00000597263.5:n.372C>T

ENST00000599021.1:n.297C>T

ENST00000600584.5:n.2636C>T

ENST00000601786.5:n.1488C>T

Uncertain Significance

BP5

BS1

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.1187C>T (p.Thr396Met) variant in MAP2K2 is present in 0.017% (11/61632) non-Finnish European alleles in gnomAD. This variant has been identified in a patient with an alternate molecular basis for disease (BP5; SCV000699629.2). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Thr396Met variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BP5.

BP5

7 month old male evaluated for Noonan Syndrome with a 20 gene RASopathy panel. Variant was identified along with pathogenic variant c.214G>T (p.Ala72Ser) in PTPN11 (VCV000013324.4) (Integrated Genetics ClinVar submission: VCV000279960.3).

BS1

.017% (11/61632) non-Finnish European alleles in gnomAD, doesn’t meet BS1

Curation History

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