NM_001164508.2(NEB):c.2540A>G (p.Asp847Gly) AND Nemaline myopathy 2

Clinical significance:Uncertain significance (Last evaluated: Sep 3, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000707620.3

Allele description [Variation Report for NM_001164508.2(NEB):c.2540A>G (p.Asp847Gly)]

NM_001164508.2(NEB):c.2540A>G (p.Asp847Gly)

Gene:
NEB:nebulin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q23.3
Genomic location:
Preferred name:
NM_001164508.2(NEB):c.2540A>G (p.Asp847Gly)
HGVS:
  • NC_000002.12:g.151687516T>C
  • NG_009382.2:g.51972A>G
  • NM_001164507.2:c.2540A>G
  • NM_001164508.2:c.2540A>GMANE SELECT
  • NM_001271208.2:c.2540A>G
  • NM_004543.5:c.2540A>G
  • NP_001157979.2:p.Asp847Gly
  • NP_001157980.2:p.Asp847Gly
  • NP_001258137.2:p.Asp847Gly
  • NP_004534.3:p.Asp847Gly
  • LRG_202t1:c.2540A>G
  • LRG_202:g.51972A>G
  • NC_000002.11:g.152544030T>C
  • NM_001271208.1:c.2540A>G
Protein change:
D847G
Links:
dbSNP: rs375894183
NCBI 1000 Genomes Browser:
rs375894183
Molecular consequence:
  • NM_001164507.2:c.2540A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001164508.2:c.2540A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001271208.2:c.2540A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004543.5:c.2540A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Nemaline myopathy 2 (NEM2)
Synonyms:
Nemaline myopathy caused by mutation in the nebulin gene; Nemaline myopathy 2, autosomal recessive
Identifiers:
MONDO: MONDO:0009725; MedGen: C1850569; OMIM: 256030

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000836721Invitaecriteria provided, single submitter
Uncertain significance
(Sep 3, 2019)
germlineclinical testing

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

SCV001452185Natera, Inc.no assertion criteria providedUncertain significance
(Jan 17, 2020)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot 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

Details of each submission

From Invitae, SCV000836721.2

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

Description

This sequence change replaces aspartic acid with glycine at codon 847 of the NEB protein (p.Asp847Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs375894183, ExAC 0.03%). This variant has not been reported in the literature in individuals with NEB-related conditions. ClinVar contains an entry for this variant (Variation ID: 516250). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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 Natera, Inc., SCV001452185.1

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

Last Updated: Nov 27, 2021

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