NM_000268.4(NF2):c.215T>C (p.Val72Ala) AND Neurofibromatosis, type 2

Clinical significance:Uncertain significance (Last evaluated: Sep 13, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000689963.4

Allele description [Variation Report for NM_000268.4(NF2):c.215T>C (p.Val72Ala)]

NM_000268.4(NF2):c.215T>C (p.Val72Ala)

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.215T>C (p.Val72Ala)
HGVS:
  • NC_000022.11:g.29636851T>C
  • NG_009057.1:g.38296T>C
  • NM_000268.3:c.215T>C
  • NM_000268.4:c.215T>CMANE SELECT
  • NM_016418.5:c.215T>C
  • NM_181825.3:c.215T>C
  • NM_181828.3:c.115-2239T>C
  • NM_181829.3:c.215T>C
  • NM_181830.3:c.115-5351T>C
  • NM_181831.3:c.115-5351T>C
  • NM_181832.3:c.215T>C
  • NM_181833.3:c.215T>C
  • NP_000259.1:p.Val72Ala
  • NP_000259.1:p.Val72Ala
  • NP_057502.2:p.Val72Ala
  • NP_861546.1:p.Val72Ala
  • NP_861967.1:p.Val72Ala
  • NP_861970.1:p.Val72Ala
  • NP_861971.1:p.Val72Ala
  • LRG_511t1:c.215T>C
  • LRG_511t2:c.215T>C
  • LRG_511:g.38296T>C
  • LRG_511p1:p.Val72Ala
  • LRG_511p2:p.Val72Ala
  • NC_000022.10:g.30032840T>C
  • NR_156186.2:n.697T>C
Protein change:
V72A
Links:
dbSNP: rs1260510937
NCBI 1000 Genomes Browser:
rs1260510937
Molecular consequence:
  • NM_181828.3:c.115-2239T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_181830.3:c.115-5351T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_181831.3:c.115-5351T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000268.3:c.215T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000268.4:c.215T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016418.5:c.215T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181825.3:c.215T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181829.3:c.215T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181832.3:c.215T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181833.3:c.215T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_156186.2:n.697T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Neurofibromatosis, type 2 (NF2)
Synonyms:
NF 2; Neurofibromatosis central type; Acoustic schwannomas bilateral; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007039; MedGen: C0027832; Orphanet: 637; OMIM: 101000

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000817636Invitaecriteria provided, single submitter
Uncertain significance
(Sep 13, 2020)
germlineclinical testing

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

SCV000839511Mendelicscriteria provided, single submitter
Uncertain significance
(Jul 2, 2018)
unknownclinical testing

Citation Link,

SCV001308953Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Apr 27, 2017)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Neurofibromatosis type 2: molecular and clinical analyses in Argentine sporadic and familial cases.

Ferrer M, Schulze A, Gonzalez S, Ferreiro V, Ciavarelli P, Otero J, Giliberto F, Basso A, Szijan I.

Neurosci Lett. 2010 Aug 9;480(1):49-54. doi: 10.1016/j.neulet.2010.05.094. Epub 2010 Jun 8.

PubMed [citation]
PMID:
20553997

Details of each submission

From Invitae, SCV000817636.3

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

Description

This sequence change replaces valine with alanine at codon 72 of the NF2 protein (p.Val72Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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

From Mendelics, SCV000839511.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Illumina Clinical Services Laboratory,Illumina, SCV001308953.1

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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

Last Updated: Oct 30, 2021

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