NM_000426.4(LAMA2):c.7691T>C (p.Leu2564Pro) AND Merosin deficient congenital muscular dystrophy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 20, 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:: RCV000015364.27

Allele description [Variation Report for NM_000426.4(LAMA2):c.7691T>C (p.Leu2564Pro)]

NM_000426.4(LAMA2):c.7691T>C (p.Leu2564Pro)

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.7691T>C (p.Leu2564Pro)

HGVS:

NC_000006.12:g.129481381T>C
NG_008678.1:g.603241T>C
NM_000426.4:c.7691T>CMANE SELECT
NM_001079823.2:c.7679T>C
NP_000417.2:p.Leu2564Pro
NP_000417.3:p.Leu2564Pro
NP_001073291.2:p.Leu2560Pro
LRG_409t1:c.7691T>C
LRG_409:g.603241T>C
LRG_409p1:p.Leu2564Pro
NC_000006.11:g.129802526T>C
NM_000426.3:c.7691T>C
P24043:p.Leu2564Pro

Protein change:

L2560P; LEU2564PRO

Links:

UniProtKB: P24043#VAR_015745; OMIM: 156225.0004; dbSNP: rs121913570

NCBI 1000 Genomes Browser:

rs121913570

Molecular consequence:

NM_000426.4:c.7691T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001079823.2:c.7679T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Merosin deficient congenital muscular dystrophy (MDC1A)
Synonyms:: Muscular dystrophy congenital, merosin negative; Congenital merosin-deficient muscular dystrophy 1A
Identifiers:: MONDO: MONDO:0011925; MedGen: C1263858; Orphanet: 258; OMIM: 607855

Recent activity

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receptor-type tyrosine-protein phosphatase mu isoform 5 [Homo sapiens]
receptor-type tyrosine-protein phosphatase mu isoform 5 [Homo sapiens]
gi|1802776458|ref|NP_001365073.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000035625	OMIM	no assertion criteria provided	Pathogenic (Oct 9, 2001)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004190533	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 20, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000035625

OMIM

no assertion criteria provided

Pathogenic
(Oct 9, 2001)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV004190533

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 20, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Congenital muscular dystrophy with primary partial laminin alpha2 chain deficiency: molecular study.

He Y, Jones KJ, Vignier N, Morgan G, Chevallay M, Barois A, Estournet-Mathiaud B, Hori H, Mizuta T, Tomé FM, North KN, Guicheney P.

Neurology. 2001 Oct 9;57(7):1319-22.

PubMed [citation]

PMID:: 11591858

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000035625.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient with congenital merosin-deficient muscular dystrophy (607855) characterized by difficulty walking, hypotonia, proximal weakness, hyporeflexia, and white matter hypodensity on MRI, He et al. (2001) identified compound heterozygosity in the LAMA2 gene: a missense mutation resulting in a leu2564-to-pro (L2564P) substitution and a nonsense mutation at codon 3085 (R3085X; 156225.0005). Laminin alpha-2 antibody labeling was mildly reduced. He et al. (2001) suggested that the patient's mild phenotype correlated with partial deficiency of laminin alpha-2 due to expression of the L2564P allele. The authors noted the importance of using antibodies against different domains of the protein for correct immunohistochemical characterization.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004190533.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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