LAMA2

laminin subunit alpha 2, the group of Laminin subunits

Basic information

Region (hg38): 6:128883138-129516566

Previous symbols: [ "LAMM" ]

Links

ENSG00000196569 ∙ NCBI:3908 ∙ OMIM:156225 ∙ HGNC:6482 ∙ Uniprot:P24043 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital merosin-deficient muscular dystrophy 1A (Supportive), mode of inheritance: AR
• congenital merosin-deficient muscular dystrophy 1A (Strong), mode of inheritance: AR
• muscular dystrophy, limb-girdle, autosomal recessive 23 (Strong), mode of inheritance: AR
• LAMA2-related muscular dystrophy (Definitive), mode of inheritance: AR
• congenital merosin-deficient muscular dystrophy 1A (Definitive), mode of inheritance: AR
• congenital merosin-deficient muscular dystrophy 1A (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Schizophrenia; Muscular dystrophy, congenital merosin-deficient, 1A; Muscular dystrophy, limb-girdle, autosomal recessive 23	AD/AR	General	In Muscular dystrophy, congenital merosin-deficient, 1A, Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing; In Schizophrenia, the evidence or clinical applicability is unclear	Musculoskeletal; Neurologic	7550355; 8887959; 8729391; 12552556; 16216942; 18700894; 20627570; 21953594; 22166137; 22675738; 23042115; 24611677; 25663498; 30055037
Clinically significant cardiomyopathy has not been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMA2 gene.

• LAMA2-related muscular dystrophy (307 variants)
• Merosin deficient congenital muscular dystrophy (78 variants)
• not provided (71 variants)
• Muscular dystrophy, limb-girdle, autosomal recessive 23 (10 variants)
• Inborn genetic diseases (8 variants)
• Abnormality of the musculature (5 variants)
• Merosin deficient congenital muscular dystrophy;Muscular dystrophy, limb-girdle, autosomal recessive 23 (4 variants)
• Muscular dystrophy, limb-girdle, autosomal recessive 23;Merosin deficient congenital muscular dystrophy (3 variants)
• Congenital muscular dystrophy due to partial LAMA2 deficiency (3 variants)
• LAMA2-related disorder (2 variants)
• Congenital Muscular Dystrophy, LAMA2-related (2 variants)
• Qualitative or quantitative defects of merosin (1 variants)
• Muscular dystrophy, congenital, merosin deficient or partially deficient (1 variants)
• Hypotonia (1 variants)
• Myalgia;Exercise-induced myalgia;Elevated circulating creatine kinase concentration (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMA2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		6	1202	16	1225
missense	4	12	1157	85	10	1268
nonsense	125	147	2			274
start loss		1				1
frameshift	185	153				338
inframe indel		2	31	1		34
splice donor/acceptor (+/-2bp)	44	141	2	1		188
splice region	2	2	84	230	9	327
non coding	1		14	715	152	882
Total	360	456	1212	2004	178

Highest pathogenic variant AF is 0.0000592

Variants in LAMA2

This is a list of pathogenic ClinVar variants found in the LAMA2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-128883143-C-T		Congenital muscular dystrophy due to partial LAMA2 deficiency	Uncertain significance (Jan 13, 2018)
6-128883147-A-G		Congenital muscular dystrophy due to partial LAMA2 deficiency	Likely benign (Jan 13, 2018)
6-128883150-AGCT-A		Congenital Muscular Dystrophy, LAMA2-related	Uncertain significance (Jun 14, 2016)
6-128883174-G-A		Congenital muscular dystrophy due to partial LAMA2 deficiency	Benign (Jul 27, 2018)
6-128883227-TC-T		not specified	Likely benign (Aug 10, 2017)
6-128883243-A-G		not specified	Uncertain significance (Jun 19, 2018)
6-128883247-T-C		LAMA2-related muscular dystrophy • Merosin deficient congenital muscular dystrophy	Pathogenic/Likely pathogenic (Jun 23, 2023)
6-128883250-C-G		LAMA2-related muscular dystrophy	Uncertain significance (Dec 03, 2021)
6-128883251-G-A		LAMA2-related muscular dystrophy	Likely benign (Oct 29, 2023)
6-128883251-G-T		LAMA2-related muscular dystrophy	Likely benign (Jul 10, 2022)
6-128883252-G-A		LAMA2-related muscular dystrophy	Uncertain significance (Apr 12, 2022)
6-128883255-GC-G		LAMA2-related muscular dystrophy	Pathogenic/Likely pathogenic (Feb 04, 2022)
6-128883257-C-G		LAMA2-related muscular dystrophy	Likely benign (Apr 14, 2022)
6-128883257-C-T		LAMA2-related muscular dystrophy	Likely benign (Sep 14, 2023)
6-128883257-CGCCGGGGTCCTCCTCCTTCTGCTGCTCTCCGGAG-C		Merosin deficient congenital muscular dystrophy	Likely pathogenic (Nov 19, 2022)
6-128883258-G-A		LAMA2-related muscular dystrophy	Conflicting classifications of pathogenicity (Jan 21, 2024)
6-128883258-G-T		LAMA2-related muscular dystrophy	Conflicting classifications of pathogenicity (Sep 28, 2023)
6-128883260-C-A		LAMA2-related muscular dystrophy	Likely benign (Dec 02, 2023)
6-128883260-C-T		LAMA2-related muscular dystrophy	Likely benign (Jan 09, 2024)
6-128883263-G-A		LAMA2-related muscular dystrophy	Likely benign (Sep 21, 2023)
6-128883263-G-C		LAMA2-related muscular dystrophy	Likely benign (Nov 07, 2023)
6-128883263-G-T		LAMA2-related muscular dystrophy	Likely benign (Oct 31, 2022)
6-128883264-G-GTCC		Merosin deficient congenital muscular dystrophy	Uncertain significance (Apr 16, 2018)
6-128883269-C-A		LAMA2-related muscular dystrophy	Likely benign (Mar 24, 2021)
6-128883269-C-T		LAMA2-related muscular dystrophy	Likely benign (Jan 13, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMA2	protein_coding	protein_coding	ENST00000421865	65	633373

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.41e-47	1.00	125331	0	417	125748	0.00166

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0300	1698	1.69e+3	1.00	0.0000948	20542
Missense in Polyphen		670	726.43	0.92232		8975
Synonymous	-1.44	666	620	1.07	0.0000363	5955
Loss of Function	4.50	102	164	0.621	0.00000948	1988

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00253	0.00253
Ashkenazi Jewish	0.00169	0.00169
East Asian	0.00403	0.00403
Finnish	0.000508	0.000508
European (Non-Finnish)	0.00169	0.00167
Middle Eastern	0.00403	0.00403
South Asian	0.00164	0.00163
Other	0.00163	0.00163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
• Disease: DISEASE: Merosin-deficient congenital muscular dystrophy 1A (MDC1A) [MIM:607855]: Characterized by difficulty walking, hypotonia, proximal weakness, hyporeflexia, and white matter hypodensity on MRI. {ECO:0000269|PubMed:11591858, ECO:0000269|PubMed:12552556, ECO:0000269|PubMed:27234031}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy;Alpha 6 Beta 4 signaling pathway;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Signal Transduction;prion pathway;Alpha6Beta4Integrin;Laminin interactions;Extracellular matrix organization;agrin in postsynaptic differentiation;a6b1 and a6b4 Integrin signaling;Non-integrin membrane-ECM interactions;ECM proteoglycans;MET activates PTK2 signaling;MET promotes cell motility;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Beta1 integrin cell surface interactions;Alpha6 beta4 integrin-ligand interactions (Consensus)

Recessive Scores

• pRec: 0.636

Intolerance Scores

• loftool: 0.948
• rvis_EVS: 0.5
• rvis_percentile_EVS: 79.64

Haploinsufficiency Scores

• pHI: 0.300
• hipred: Y
• hipred_score: 0.680
• ghis: 0.517

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.513

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lama2
• Phenotype: hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; endocrine/exocrine gland phenotype; muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: lama2
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: detached from

Gene ontology

• Biological process: cell adhesion;axon guidance;muscle organ development;Schwann cell differentiation;regulation of cell adhesion;extracellular matrix organization;regulation of cell migration;positive regulation of synaptic transmission, cholinergic;regulation of embryonic development
• Cellular component: extracellular region;basement membrane;neuromuscular junction;sarcolemma;synaptic cleft;dendritic spine;collagen-containing extracellular matrix
• Molecular function: signaling receptor binding;structural molecule activity;extracellular matrix structural constituent