NM_001164508.2(NEB):c.13052A>G (p.Gln4351Arg) AND Nemaline myopathy 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 22, 2016
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:: RCV000536275.2

Allele description [Variation Report for NM_001164508.2(NEB):c.13052A>G (p.Gln4351Arg)]

NM_001164508.2(NEB):c.13052A>G (p.Gln4351Arg)

Gene:

NEB:nebulin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q23.3

Genomic location:

Preferred name:

NM_001164508.2(NEB):c.13052A>G (p.Gln4351Arg)

HGVS:

NC_000002.12:g.151604567T>C
NG_009382.2:g.134921A>G
NM_001164507.2:c.13052A>G
NM_001164508.2:c.13052A>GMANE SELECT
NM_001271208.2:c.13052A>G
NM_004543.5:c.11601+5242A>G
NP_001157979.2:p.Gln4351Arg
NP_001157980.2:p.Gln4351Arg
NP_001258137.2:p.Gln4351Arg
LRG_202t1:c.13052A>G
LRG_202:g.134921A>G
NC_000002.11:g.152461081T>C
NM_001271208.1:c.13052A>G

Protein change:

Q4351R

Links:

dbSNP: rs1553871396

NCBI 1000 Genomes Browser:

rs1553871396

Molecular consequence:

NM_004543.5:c.11601+5242A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001164507.2:c.13052A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001164508.2:c.13052A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001271208.2:c.13052A>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000640547	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 22, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000640547

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 22, 2016)

germline

clinical testing

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

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	clinical 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, SCV000640547.2

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

Description

This sequence change replaces glutamine with arginine at codon 4351 of the NEB protein (p.Gln4351Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. This variant occurs in a region of NEB (Exons 82-105) consisting of three highly homologous 8-exon repeat units (exons 82-89, exons 90-97, exons 98-105). Sequence variants in this region can be detected, but this assay cannot determine which of the three repeat units is affected, and zygosity is often ambiguous. All variants in this region are reported relative to the exon 82-89 repeat. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change. In summary, this variant is a novel missense change that is not predicted to affect protein function. Missense variants in the NEB gene are typically not pathogenic, and there is no indication that this variant causes disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Mar 26, 2023

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