NM_030662.4(MAP2K2):c.1074G>A (p.Ala358=) AND not specified

Germline classification:: Benign (3 submissions)
Last evaluated:: Sep 2, 2018
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:: RCV000254049.7

Allele description [Variation Report for NM_030662.4(MAP2K2):c.1074G>A (p.Ala358=)]

NM_030662.4(MAP2K2):c.1074G>A (p.Ala358=)

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.1074G>A (p.Ala358=)

Other names:

NM_030662.3(MAP2K2):c.1074G>A

HGVS:

NC_000019.10:g.4094471C>T
NG_007996.1:g.34658G>A
NM_030662.4:c.1074G>AMANE SELECT
NP_109587.1:p.Ala358=
NP_109587.1:p.Ala358=
LRG_750t1:c.1074G>A
LRG_750:g.34658G>A
LRG_750p1:p.Ala358=
NC_000019.9:g.4094469C>T
NM_030662.3:c.1074G>A
p.Ala358Ala

Links:

dbSNP: rs140896887

NCBI 1000 Genomes Browser:

rs140896887

Molecular consequence:

NM_030662.4:c.1074G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

Clear Turn Off Turn On

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
SCV000314683	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000513531	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Sep 8, 2015)	germline	clinical testing	Citation Link,
SCV000917613	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Sep 2, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000314683

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000513531

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Benign
(Sep 8, 2015)

germline

clinical testing

Citation Link,

SCV000917613

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Sep 2, 2018)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV000314683.1

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

#	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

From GeneDx, SCV000513531.4

#	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, SCV000917613.1

#	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.1074G>A 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 0.00021 in 203332 control chromosomes, predominantly at a frequency of 0.0021 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 840-folds higher than 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 a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.1074G>A in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely benign/benign. 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: May 1, 2024

ClinVar

Relating variation to medicine