NM_000426.3(LAMA2):c.5562+5G>C AND Laminin alpha 2-related dystrophy

Clinical significance:Pathogenic (Last evaluated: Sep 2, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000700168.3

Allele description [Variation Report for NM_000426.3(LAMA2):c.5562+5G>C]

NM_000426.3(LAMA2):c.5562+5G>C

Gene:
LAMA2:laminin subunit alpha 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q22.33
Genomic location:
Preferred name:
NM_000426.3(LAMA2):c.5562+5G>C
HGVS:
  • NC_000006.12:g.129401345G>C
  • NG_008678.1:g.523205G>C
  • NM_000426.3:c.5562+5G>C
  • NM_001079823.2:c.5562+5G>C
  • LRG_409t1:c.5562+5G>C
  • LRG_409:g.523205G>C
  • NC_000006.11:g.129722490G>C
Links:
dbSNP: rs771046502
NCBI 1000 Genomes Browser:
rs771046502
Molecular consequence:
  • NM_000426.3:c.5562+5G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001079823.2:c.5562+5G>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Laminin alpha 2-related dystrophy (LAMA2-RD)
Identifiers:
MedGen: CN117977

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000828913Invitaecriteria provided, single submitter
Pathogenic
(Sep 2, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in the laminin alpha2-chain gene in two children with early-onset muscular dystrophy.

Naom I, D'alessandro M, Sewry CA, Jardine P, Ferlini A, Moss T, Dubowitz V, Muntoni F.

Brain. 2000 Jan;123 ( Pt 1):31-41.

PubMed [citation]
PMID:
10611118

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
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000828913.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change falls in intron 38 of the LAMA2 gene. It does not directly change the encoded amino acid sequence of the LAMA2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs771046502, ExAC 0.003%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with muscular dystrophy (PMID: 10611118). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant has been reported as homozygous or in combination with another LAMA2 variant in individuals affected with muscular dystrophy (PMID: 10611118, 20207543, 12552556). This variant is also known as IVS37+5G>C or c.5611+5G>C in the literature. ClinVar contains an entry for this variant (Variation ID: 197024). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 10, 2021

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