NM_030662.4(MAP2K2):c.619G>A (p.Glu207Lys) AND RASopathy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 12, 2022
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:: RCV000158024.9

Allele description [Variation Report for NM_030662.4(MAP2K2):c.619G>A (p.Glu207Lys)]

NM_030662.4(MAP2K2):c.619G>A (p.Glu207Lys)

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.619G>A (p.Glu207Lys)

Other names:

p.E207K:GAG>AAG; NM_030662.3(MAP2K2):c.619G>A

HGVS:

NC_000019.10:g.4101105C>T
NG_007996.1:g.28024G>A
NM_030662.4:c.619G>AMANE SELECT
NP_109587.1:p.Glu207Lys
NP_109587.1:p.Glu207Lys
LRG_750t1:c.619G>A
LRG_750:g.28024G>A
LRG_750p1:p.Glu207Lys
NC_000019.9:g.4101103C>T
NM_030662.3:c.619G>A

Protein change:

E207K

Links:

dbSNP: rs727504382

NCBI 1000 Genomes Browser:

rs727504382

Molecular consequence:

NM_030662.4:c.619G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000606945	GenomeConnect, ClinGen	no classification provided	not provided	unknown	phenotyping only
SCV000815593	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 12, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33452774, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000606945

GenomeConnect, ClinGen

no classification provided

not provided

unknown

phenotyping only

SCV000815593

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 12, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	phenotyping only

Citations

PubMed

Mutation and Phenotypic Spectrum of Patients With RASopathies.

Lallar M, Bijarnia-Mahay S, Verma IC, Mandal K, Puri RD.

Indian Pediatr. 2021 Jan 15;58(1):30-33.

PubMed [citation]

PMID:: 33452774

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 GenomeConnect, ClinGen, SCV000606945.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	phenotyping only	not provided

Description

GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	validation		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000815593.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 207 of the MAP2K2 protein (p.Glu207Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of MAP2K2-related conditions (PMID: 33452774; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 40813). 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) performed at Invitae indicates that this missense variant is expected to disrupt MAP2K2 protein function.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 22, 2024

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