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NM_030662.4(MAP2K2):c.391G>A (p.Val131Met) AND RASopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 11, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003764692.2

Allele description [Variation Report for NM_030662.4(MAP2K2):c.391G>A (p.Val131Met)]

NM_030662.4(MAP2K2):c.391G>A (p.Val131Met)

Gene:
MAP2K2:mitogen-activated protein kinase kinase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.3
Genomic location:
Preferred name:
NM_030662.4(MAP2K2):c.391G>A (p.Val131Met)
HGVS:
  • NC_000019.10:g.4110568C>T
  • NG_007996.1:g.18561G>A
  • NM_030662.4:c.391G>AMANE SELECT
  • NP_109587.1:p.Val131Met
  • NP_109587.1:p.Val131Met
  • LRG_750t1:c.391G>A
  • LRG_750:g.18561G>A
  • LRG_750p1:p.Val131Met
  • NC_000019.9:g.4110566C>T
  • NM_030662.3:c.391G>A
  • c.391G>A
Protein change:
V131M
Links:
dbSNP: rs397517413
NCBI 1000 Genomes Browser:
rs397517413
Molecular consequence:
  • NM_030662.4:c.391G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
RASopathy
Synonyms:
rasopathies; Noonan spectrum disorder
Identifiers:
MONDO: MONDO:0021060; MedGen: C5555857

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004667167Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 11, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Retrospective study of prenatal ultrasound findings in newborns with a Noonan spectrum disorder.

Hakami F, Dillon MW, Lebo M, Mason-Suares H.

Prenat Diagn. 2016 May;36(5):418-23. doi: 10.1002/pd.4797. Epub 2016 Mar 28.

PubMed [citation]
PMID:
26918529

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004667167.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 131 of the MAP2K2 protein (p.Val131Met). This variant is present in population databases (rs397517413, gnomAD 0.007%). This missense change has been observed in individual(s) with clinical features of MAP2K2-related conditions (PMID: 26918529). ClinVar contains an entry for this variant (Variation ID: 46234). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MAP2K2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024