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]

Link to SEPIO compliant JSON-LD document

Variant: NM_030662.3(MAP2K2):c.281C>T (p.Ser94Leu)

CA180967

40786 (ClinVar)

Gene: MAP2K2

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 2ae26f96-8b07-456f-9375-37c36e0c6d97

HGVS expressions

NM_030662.3:c.281C>T

NM_030662.3(MAP2K2):c.281C>T (p.Ser94Leu)

NC_000019.10:g.4117441G>A

CM000681.2:g.4117441G>A

NC_000019.9:g.4117439G>A

CM000681.1:g.4117439G>A

NC_000019.8:g.4068439G>A

NG_007996.1:g.11688C>T

NM_030662.4:c.281C>T

ENST00000262948.9:c.281C>T

ENST00000394867.8:c.-11C>T

ENST00000599345.1:n.478C>T

Uncertain Significance

PP3 PP2

BS1 BS2

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.281C>T (p.Ser94Leu) variant in MAP2K2 has been identified in 2 independent occurrences in patients with a RASopathy; however, in both cases it was inherited from an apparently unaffected parent (BS2 not met; GeneDx, LMM internal data; ClinVar SCV000204231.4; SCV000207977.8). The p.Ser94Leu variant was present in 0.012% (3/24906) of African alleles in gnomAD (PM2 not met, gnomad.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 this variant may impact protein function (PP3). In summary, the clinical significance of the p.Ser94Leu variant is uncertain. ACMG/AMP criteria applied: PP2, PP3.

PP3

Computational prediction tools and conservation analysis suggest that this variant may impact protein function (PP3).

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).

BS1

The p.Ser94Leu variant was present in 0.012% (3/24906) of African alleles in gnomAD (PM2 not met, gnomad.broadinstitute.org).

BS2

Seen in 2 unaffected parents of 2 different probands (Laboratory for Molecular medicine internal data, ClinVar SCV000204231.4)

Approved on: 2020-05-18

Published on: 2020-07-01

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