NM_030662.4(MAP2K2):c.1140C>T (p.Ala380=) AND not specified

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Mar 18, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000043643.8

Allele description [Variation Report for NM_030662.4(MAP2K2):c.1140C>T (p.Ala380=)]

NM_030662.4(MAP2K2):c.1140C>T (p.Ala380=)

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.1140C>T (p.Ala380=)

Other names:

p.A380A:GCC>GCT; NM_030662.3(MAP2K2):c.1140C>T

HGVS:

NC_000019.10:g.4090661G>A
NG_007996.1:g.38468C>T
NM_030662.4:c.1140C>TMANE SELECT
NP_109587.1:p.Ala380=
NP_109587.1:p.Ala380=
LRG_750t1:c.1140C>T
LRG_750:g.38468C>T
LRG_750p1:p.Ala380=
NC_000019.9:g.4090659G>A
NM_030662.3:c.1140C>T
c.1140C>T
p.Ala380Ala

Links:

dbSNP: rs146618055

NCBI 1000 Genomes Browser:

rs146618055

Molecular consequence:

NM_030662.4:c.1140C>T - synonymous variant - [Sequence Ontology: SO:0001819]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Lipogramma klayi isolate DOM16152 cytochrome oxidase subunit I (COI) gene, parti...
Lipogramma klayi isolate DOM16152 cytochrome oxidase subunit I (COI) gene, partial cds; mitochondrial
gi|1147541940|gb|KX713821.1|

Nucleotide
Homologene neighbors for GEO Profiles (Select 120317332) (0)
GEO Profiles
Profile neighbors for GEO Profiles (Select 131322727) (199)
GEO Profiles
Profile neighbors for GEO Profiles (Select 131328127) (199)
GEO Profiles
Profile neighbors for GEO Profiles (Select 131345444) (199)
GEO Profiles

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000063156	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Oct 18, 2012)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22558107, 24033266
SCV000207953	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Aug 26, 2014)	germline	clinical testing	Citation Link,
SCV001363490	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Mar 18, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000063156

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely benign
(Oct 18, 2012)

germline

clinical testing

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

SCV000207953

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Benign
(Aug 26, 2014)

germline

clinical testing

Citation Link,

SCV001363490

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Mar 18, 2019)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	2	2	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.

Kelleher RJ 3rd, Geigenmüller U, Hovhannisyan H, Trautman E, Pinard R, Rathmell B, Carpenter R, Margulies D.

PLoS One. 2012;7(4):e35003. doi: 10.1371/journal.pone.0035003. Epub 2012 Apr 27.

PubMed [citation]

PMID:: 22558107
PMCID:: PMC3338748

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000063156.6

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

Description

Ala380Ala in exon 11 of MAP2K2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located ne ar a splice junction. In addition, this variant was identified via high-throughp ut sequencing in controls (MAF<1%) and presumed to be benign (Kelleher 2012).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		2	not provided	2	not provided

From GeneDx, SCV000207953.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363490.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: MAP2K2 c.1140C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00023 in 192890 control chromosomes. The observed variant frequency is approximately 93 fold of the estimated maximal expected allele frequency for a pathogenic variant in MAP2K2 causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1140C>T in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. One expert panel has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Two other labs in ClinVar classified the variant as benign and likely benign respectively in 2014. Based on the evidence outlined above, the variant was classified as benign.

#	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: Oct 13, 2024

ClinVar

Relating variation to medicine