NM_001164508.2(NEB):c.10021G>T (p.Ala3341Ser) AND Nemaline myopathy 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 28, 2021
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:: RCV000818842.4

Allele description [Variation Report for NM_001164508.2(NEB):c.10021G>T (p.Ala3341Ser)]

NM_001164508.2(NEB):c.10021G>T (p.Ala3341Ser)

Gene:

NEB:nebulin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q23.3

Genomic location:

Preferred name:

NM_001164508.2(NEB):c.10021G>T (p.Ala3341Ser)

HGVS:

NC_000002.12:g.151627645C>A
NG_009382.2:g.111843G>T
NM_001164507.2:c.10021G>T
NM_001164508.2:c.10021G>TMANE SELECT
NM_001271208.2:c.10021G>T
NM_004543.5:c.9292G>T
NP_001157979.2:p.Ala3341Ser
NP_001157980.2:p.Ala3341Ser
NP_001258137.2:p.Ala3341Ser
NP_004534.3:p.Ala3098Ser
LRG_202t1:c.10021G>T
LRG_202:g.111843G>T
NC_000002.11:g.152484159C>A
NM_001271208.1:c.10021G>T

Protein change:

A3098S

Links:

dbSNP: rs1574279999

NCBI 1000 Genomes Browser:

rs1574279999

Molecular consequence:

NM_001164507.2:c.10021G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164508.2:c.10021G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001271208.2:c.10021G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004543.5:c.9292G>T - 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
SCV000959476	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002077139	Natera, Inc.	no assertion criteria provided	Uncertain significance (Nov 5, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000959476

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2021)

germline

clinical testing

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

SCV002077139

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Nov 5, 2020)

germline

clinical testing

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, SCV000959476.2

#	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 alanine with serine at codon 3341 of the NEB protein (p.Ala3341Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NEB-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.

#	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 Natera, Inc., SCV002077139.1

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

#	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: Feb 7, 2023

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