NM_000426.4(LAMA2):c.5290dup (p.Glu1764fs) AND LAMA2-related muscular dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 3, 2022
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:: RCV000796627.15

Allele description [Variation Report for NM_000426.4(LAMA2):c.5290dup (p.Glu1764fs)]

NM_000426.4(LAMA2):c.5290dup (p.Glu1764fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

6q22.33

Genomic location:

Preferred name:

NM_000426.4(LAMA2):c.5290dup (p.Glu1764fs)

HGVS:

NC_000006.12:g.129393100dup
NG_008678.1:g.514960dup
NM_000426.4:c.5290dupMANE SELECT
NM_001079823.2:c.5290dup
NP_000417.2:p.Glu1764fs
NP_000417.3:p.Glu1764fs
NP_001073291.2:p.Glu1764fs
LRG_409t1:c.5290dup
LRG_409:g.514960dup
LRG_409p1:p.Glu1764fs
NC_000006.11:g.129714239_129714240insG
NC_000006.11:g.129714245dup
NC_000006.12:g.129393094_129393095insG
NM_000426.3:c.5290dup
NM_000426.3:c.5290dupG

Protein change:

E1764fs

Links:

dbSNP: rs1415944134

NCBI 1000 Genomes Browser:

rs1415944134

Molecular consequence:

NM_000426.4:c.5290dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079823.2:c.5290dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000936147	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20207543, 30301903, 18700894, 32904964, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000936147

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2022)

germline

clinical testing

PubMed (5)
[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

Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations.

Geranmayeh F, Clement E, Feng LH, Sewry C, Pagan J, Mein R, Abbs S, Brueton L, Childs AM, Jungbluth H, De Goede CG, Lynch B, Lin JP, Chow G, Sousa Cd, O'Mahony O, Majumdar A, Straub V, Bushby K, Muntoni F.

Neuromuscul Disord. 2010 Apr;20(4):241-50. doi: 10.1016/j.nmd.2010.02.001. Epub 2010 Mar 6.

PubMed [citation]

PMID:: 20207543

Deletion of exon 4 in LAMA2 is the most frequent mutation in Chinese patients with laminin α2-related muscular dystrophy.

Ge L, Liu A, Gao K, Du R, Ding J, Mao B, Hua Y, Zhang X, Tan D, Yang H, Fu X, Fan Y, Zhang L, Song S, Wu J, Zhang F, Jiang Y, Wu X, Xiong H.

Sci Rep. 2018 Oct 9;8(1):14989. doi: 10.1038/s41598-018-33098-3.

PubMed [citation]

PMID:: 30301903
PMCID:: PMC6177444

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV000936147.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 631972). This premature translational stop signal has been observed in individuals with autosomal recessive congenital muscular dystrophy (PMID: 20207543, 30301903). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu1764Glyfs*3) 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).

#	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: Apr 15, 2024

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