NM_000426.4(LAMA2):c.7147C>T (p.Arg2383Ter) AND LAMA2-related muscular dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 5, 2023
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:: RCV000654712.8

Allele description [Variation Report for NM_000426.4(LAMA2):c.7147C>T (p.Arg2383Ter)]

NM_000426.4(LAMA2):c.7147C>T (p.Arg2383Ter)

Gene:

LAMA2:laminin subunit alpha 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q22.33

Genomic location:

Preferred name:

NM_000426.4(LAMA2):c.7147C>T (p.Arg2383Ter)

HGVS:

NC_000006.12:g.129464444C>T
NG_008678.1:g.586304C>T
NM_000426.4:c.7147C>TMANE SELECT
NM_001079823.2:c.7147C>T
NP_000417.2:p.Arg2383Ter
NP_000417.3:p.Arg2383Ter
NP_001073291.2:p.Arg2383Ter
LRG_409t1:c.7147C>T
LRG_409:g.586304C>T
LRG_409p1:p.Arg2383Ter
NC_000006.11:g.129785589C>T
NM_000426.3:c.7147C>T
NP_000417.2:p.Arg2383*

Protein change:

R2383*; ARG2383TER

Links:

OMIM: 156225.0012; dbSNP: rs121913576

NCBI 1000 Genomes Browser:

rs121913576

Molecular consequence:

NM_000426.4:c.7147C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001079823.2:c.7147C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: LAMA2-related muscular dystrophy (LAMA2-RD)
Synonyms:: Laminin alpha 2-related dystrophy
Identifiers:: MONDO: MONDO:0100228; MedGen: C5679788

Recent activity

Clear Turn Off Turn On

PREDICTED: hepatocyte growth factor receptor isoform X2 [Chinchilla lanigera]
PREDICTED: hepatocyte growth factor receptor isoform X2 [Chinchilla lanigera]
gi|533147568|ref|XP_005388180.1|

Protein
Aicardi-Goutieres syndrome 2
Aicardi-Goutieres syndrome 2

MedGen
RNASEH2B (2)
MedGen

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
SCV000776611	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 5, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 18700894, 32904964, 11071490, 24223650, 24611677, 30055037, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000776611

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 5, 2023)

germline

clinical testing

PubMed (7)
[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

LAMA2 gene analysis in a cohort of 26 congenital muscular dystrophy patients.

Oliveira J, Santos R, Soares-Silva I, Jorge P, Vieira E, Oliveira ME, Moreira A, Coelho T, Ferreira JC, Fonseca MJ, Barbosa C, Prats J, Aríztegui ML, Martins ML, Moreno T, Heinimann K, Barbot C, Pascual-Pascual SI, Cabral A, Fineza I, Santos M, Bronze-da-Rocha E.

Clin Genet. 2008 Dec;74(6):502-12. doi: 10.1111/j.1399-0004.2008.01068.x. Epub 2008 Jun 11.

PubMed [citation]

PMID:: 18700894

Limb girdle muscular dystrophy due to LAMA2 gene mutations: new mutations expand the clinical spectrum of a still challenging diagnosis.

Magri F, Brusa R, Bello L, Peverelli L, Del Bo R, Govoni A, Cinnante C, Colombo I, Fortunato F, Tironi R, Corti S, Grimoldi N, Sciacco M, Bresolin N, Pegoraro E, Moggio M, Comi GP.

Acta Myol. 2020 Jun;39(2):67-82. doi: 10.36185/2532-1900-009.

PubMed [citation]

PMID:: 32904964
PMCID:: PMC7460730

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000776611.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Arg2383*) in the LAMA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMA2 are known to be pathogenic (PMID: 18700894, 32904964). This variant is present in population databases (rs121913576, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with congenital muscular dystrophy (PMID: 11071490, 24223650, 24611677, 30055037). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 14300). 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: Jun 17, 2024

ClinVar

Relating variation to medicine