NM_001164508.2(NEB):c.3255+1G>T AND Nemaline myopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 18, 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:: RCV001199936.1

Allele description [Variation Report for NM_001164508.2(NEB):c.3255+1G>T]

NM_001164508.2(NEB):c.3255+1G>T

Gene:

NEB:nebulin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q23.3

Genomic location:

Preferred name:

NM_001164508.2(NEB):c.3255+1G>T

HGVS:

NC_000002.12:g.151679720C>A
NG_009382.2:g.59768G>T
NM_001164507.2:c.3255+1G>T
NM_001164508.2:c.3255+1G>TMANE SELECT
NM_001271208.2:c.3255+1G>T
NM_004543.5:c.3255+1G>T
LRG_202t1:c.3255+1G>T
LRG_202:g.59768G>T
NC_000002.11:g.152536234C>A
NM_001271208.1:c.3255+1G>T

Links:

dbSNP: rs375628303

NCBI 1000 Genomes Browser:

rs375628303

Molecular consequence:

NM_001164507.2:c.3255+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001164508.2:c.3255+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001271208.2:c.3255+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_004543.5:c.3255+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Nemaline myopathy
Synonyms:: Myopathies, Nemaline; Rod myopathy
Identifiers:: MONDO: MONDO:0018958; MedGen: C0206157; OMIM: PS161800

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001370723	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (May 18, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25205138, 16917880 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001370723

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(May 18, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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	clinical testing

Citations

PubMed

Mutation update: the spectra of nebulin variants and associated myopathies.

Lehtokari VL, Kiiski K, Sandaradura SA, Laporte J, Repo P, Frey JA, Donner K, Marttila M, Saunders C, Barth PG, den Dunnen JT, Beggs AH, Clarke NF, North KN, Laing NG, Romero NB, Winder TL, Pelin K, Wallgren-Pettersson C.

Hum Mutat. 2014 Dec;35(12):1418-26. doi: 10.1002/humu.22693.

PubMed [citation]

PMID:: 25205138
PMCID:: PMC4295925

Identification of 45 novel mutations in the nebulin gene associated with autosomal recessive nemaline myopathy.

Lehtokari VL, Pelin K, Sandbacka M, Ranta S, Donner K, Muntoni F, Sewry C, Angelini C, Bushby K, Van den Bergh P, Iannaccone S, Laing NG, Wallgren-Pettersson C.

Hum Mutat. 2006 Sep;27(9):946-56.

PubMed [citation]

PMID:: 16917880

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001370723.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: NEB c.3255+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5 splicing donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing and results in skipping of exon 32 (Lehtokari_2006). The variant allele was found at a frequency of 4e-06 in 248154 control chromosomes (gnomAD and publication). c.3255+1G>T has been reported in the literature in multiple individuals affected with Nemaline Myopathy (Lehtokari_2006, Lehtokari_2014). These data indicate that the variant is very likely to be associated with disease. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic (2x) and likely pathogenic (1x). Based on the evidence outlined above, the variant was classified as pathogenic.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine