NM_170707.4(LMNA):c.937-11C>G AND Charcot-Marie-Tooth disease type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 8, 2024
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:: RCV001854178.3

Allele description [Variation Report for NM_170707.4(LMNA):c.937-11C>G]

NM_170707.4(LMNA):c.937-11C>G

Gene:

LMNA:lamin A/C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_170707.4(LMNA):c.937-11C>G

HGVS:

NC_000001.11:g.156135890C>G
NG_008692.2:g.58318C>G
NM_001257374.3:c.601-11C>G
NM_001282624.2:c.694-11C>G
NM_001282625.2:c.937-11C>G
NM_001282626.2:c.937-11C>G
NM_005572.4:c.937-11C>G
NM_170707.4:c.937-11C>GMANE SELECT
NM_170708.4:c.937-11C>G
LRG_254t2:c.937-11C>G
LRG_254:g.58318C>G
NC_000001.10:g.156105681C>G
NM_170707.2:c.937-11C>G

Links:

dbSNP: rs267607645

NCBI 1000 Genomes Browser:

rs267607645

Molecular consequence:

NM_001257374.3:c.601-11C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001282624.2:c.694-11C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001282625.2:c.937-11C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001282626.2:c.937-11C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_005572.4:c.937-11C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_170707.4:c.937-11C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_170708.4:c.937-11C>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Charcot-Marie-Tooth disease type 2
Synonyms:: Charcot-Marie-Tooth, Type 2
Identifiers:: MONDO: MONDO:0018993; MedGen: C0270914

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
SCV002153336	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 8, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21462202, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002153336

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 8, 2024)

germline

clinical testing

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

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

Aberrant splicing in the LMNA gene caused by a novel mutation on the polypyrimidine tract of intron 5.

Carboni N, Floris M, Mateddu A, Porcu M, Marrosu G, Solla E, Cocco E, Mura M, Marini S, Maioli MA, Piras R, Aste R, Marrosu MG.

Muscle Nerve. 2011 May;43(5):688-93. doi: 10.1002/mus.21937. Epub 2011 Apr 1.

PubMed [citation]

PMID:: 21462202

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002153336.3

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

Description

This sequence change falls in intron 5 of the LMNA gene. It does not directly change the encoded amino acid sequence of the LMNA protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with autosomal dominant limb-girdle muscular dystrophy (PMID: 21462202). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 66957). Studies have shown that this variant results in altered splicing and introduces a premature termination codon (PMID: 21462202). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been 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: Feb 20, 2024

ClinVar

Relating variation to medicine