NM_000268.4(NF2):c.1232G>A (p.Arg411His) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 22, 2020
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:: RCV001249076.3

Allele description [Variation Report for NM_000268.4(NF2):c.1232G>A (p.Arg411His)]

NM_000268.4(NF2):c.1232G>A (p.Arg411His)

Gene:

NF2:NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q12.2

Genomic location:

Preferred name:

NM_000268.4(NF2):c.1232G>A (p.Arg411His)

HGVS:

NC_000022.11:g.29673378G>A
NG_009057.1:g.74823G>A
NM_000268.4:c.1232G>AMANE SELECT
NM_016418.5:c.1232G>A
NM_181825.3:c.1232G>A
NM_181828.3:c.1106G>A
NM_181829.3:c.1109G>A
NM_181830.3:c.983G>A
NM_181831.3:c.983G>A
NM_181832.3:c.1232G>A
NM_181833.3:c.448-21374G>A
NP_000259.1:p.Arg411His
NP_000259.1:p.Arg411His
NP_057502.2:p.Arg411His
NP_861546.1:p.Arg411His
NP_861966.1:p.Arg369His
NP_861967.1:p.Arg370His
NP_861968.1:p.Arg328His
NP_861969.1:p.Arg328His
NP_861970.1:p.Arg411His
LRG_511t1:c.1232G>A
LRG_511t2:c.1232G>A
LRG_511:g.74823G>A
LRG_511p1:p.Arg411His
LRG_511p2:p.Arg411His
NC_000022.10:g.30069367G>A
NM_000268.3(NF2):c.1232G>A
NM_000268.3:c.1232G>A
NR_156186.2:n.1714G>A
p.Arg411His

Protein change:

R328H

Links:

dbSNP: rs201214090

NCBI 1000 Genomes Browser:

rs201214090

Molecular consequence:

NM_181833.3:c.448-21374G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000268.4:c.1232G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016418.5:c.1232G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181825.3:c.1232G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181828.3:c.1106G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181829.3:c.1109G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181830.3:c.983G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181831.3:c.983G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181832.3:c.1232G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_156186.2:n.1714G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001423027	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 22, 2020)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001423027

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 22, 2020)

germline

curation

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

Citation Link

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	curation

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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001423027.2

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

Description

The p.Arg411His variant in NF2 has not been previously reported in individuals with Neurofibromatosis but has been identified in 0.01181% (4/33872) of Latino chromosomes, 0.003403% (1/29382) of South Asian chromosomes, and 0.0009079% (1/110142) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs201214090). This variant has also been reported as a VUS in ClinVar (Variation ID: 527695). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. One additional variant, resulting in a different amino acid change at the same position, p.Arg411Cys, has been reported as a VUS in association with disease in ClinVar (Variation ID: 567682). In summary, while the clinical significance of the p.Arg411His variant is uncertain, these data suggest that it is more likely to be benign. ACMG/AMP Criteria applied: BS1 (Richards 2015).

#	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 8, 2024

ClinVar

Relating variation to medicine