The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

Variant: NM_030662.3(MAP2K2):c.806C>G (p.Pro269Arg)

CA180914

177876 (ClinVar)

Gene: MAP2K2
Condition: RASopathy
Inheritance Mode: Autosomal dominant inheritance
UUID: 4aa8ed55-4b35-4739-9e18-4c63fd36145a
Approved on: 2020-03-09
Published on: 2020-03-09

HGVS expressions

NM_030662.3:c.806C>G
NM_030662.3(MAP2K2):c.806C>G (p.Pro269Arg)
NC_000019.10:g.4099314G>C
CM000681.2:g.4099314G>C
NC_000019.9:g.4099312G>C
CM000681.1:g.4099312G>C
NC_000019.8:g.4050312G>C
NG_007996.1:g.29815C>G
NM_030662.4:c.806C>G
ENST00000262948.9:c.806C>G
ENST00000394867.8:c.515C>G
ENST00000593364.5:n.753C>G
ENST00000595715.1:n.621C>G
ENST00000597263.5:n.169+1705C>G
ENST00000599021.1:n.29+1705C>G
ENST00000600584.5:n.1366C>G
ENST00000601786.5:n.1107C>G
More

Uncertain Significance

Met criteria codes 3
PP3 PM2 BP5
Not Met criteria codes 1
BS2

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
RASopathy VCEP
The c.806C>G (p.Pro269Arg) variant in MAP2K2 is absent from gnomAD (PM2). This variant has been observed in an individual with an alternate mechanism of disease (VCV000013329.8; Laboratory for Molecular Medicine internal data; BP5). Four apparently unaffected parental samples involved in whole exome testing were observed with this variant supporting that this variant is likely benign; however, this evidence does not meet current scoring criteria for BS2 at this time. Computational prediction tools and conservation analysis suggest that the p.Pro269Arg variant may impact the protein (PP3). In summary, the clinical significance of the p.Pro269Arg variant is uncertain. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): PP3, PM2, BP5.
Met criteria codes
PP3
Although the REVEL score is .71, which is above the threshold to apply PP3
PM2
Absent from gnomAD
BP5
4yo white male het. for this variant. Had diagnostic testing for NS. Also het. for c.184T>G (p.Tyr62Asp) in PTPN11, Path in ClinVar (ID: 13329) by 15 submitters w/o conflict (Laboratory for Molecular Medicine internal data)
Not Met criteria codes
BS2
GeneDx: Identified by whole exome in 4 unaffected parents from 4 different trios (SCV000808657.1)
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.