LAMC2

laminin subunit gamma 2, the group of Laminin subunits

Basic information

Region (hg38): 1:183186238-183245127

Previous symbols: [ "EBR2", "LAMB2T", "LAMNB2", "EBR2A" ]

Links

ENSG00000058085 ∙ NCBI:3918 ∙ OMIM:150292 ∙ HGNC:6493 ∙ Uniprot:Q13753 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• junctional epidermolysis bullosa (Definitive), mode of inheritance: AR
• junctional epidermolysis bullosa Herlitz type (Strong), mode of inheritance: AR
• junctional epidermolysis bullosa, non-Herlitz type (Strong), mode of inheritance: AR
• junctional epidermolysis bullosa Herlitz type (Strong), mode of inheritance: AR
• junctional epidermolysis bullosa, non-Herlitz type (Strong), mode of inheritance: AR
• generalized junctional epidermolysis bullosa non-Herlitz type (Supportive), mode of inheritance: AR
• junctional epidermolysis bullosa Herlitz type (Supportive), mode of inheritance: AR
• junctional epidermolysis bullosa Herlitz type (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epidermolysis bullosa, junctional 3A, intermediate; Epidermolysis bullosa, junctional 3B, severe	AR	General	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	Dermatologic	8012393; 11810295; 16473856; 21198797; 21801158

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMC2 gene.

• not provided (74 variants)
• Junctional epidermolysis bullosa (7 variants)
• Epidermolysis bullosa, junctional 3B, severe (4 variants)
• Junctional epidermolysis bullosa gravis of Herlitz (4 variants)
• Junctional epidermolysis bullosa, non-Herlitz type (3 variants)
• Epidermolysis bullosa, junctional 3A, intermediate (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMC2 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			2	430	9	441
missense	2		111	18	9	140
nonsense	38	41				79
start loss	1	1				2
frameshift	36	36				72
inframe indel			5	1		6
splice donor/acceptor (+/-2bp)	5	37	1			43
splice region	1		4	68	1	74
non coding			37	149	63	249
Total	82	115	156	598	81

Highest pathogenic variant AF is 0.00000657

Variants in LAMC2

This is a list of pathogenic ClinVar variants found in the LAMC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-183186264-A-G		Junctional epidermolysis bullosa • Junctional epidermolysis bullosa, non-Herlitz type • Junctional epidermolysis bullosa gravis of Herlitz	Benign (Jul 08, 2021)
1-183186274-G-A		Junctional epidermolysis bullosa	Uncertain significance (Jan 12, 2018)
1-183186314-C-T		Junctional epidermolysis bullosa	Uncertain significance (Jan 13, 2018)
1-183186315-C-G		Junctional epidermolysis bullosa	Benign (May 13, 2021)
1-183186338-C-T		Junctional epidermolysis bullosa • Junctional epidermolysis bullosa gravis of Herlitz	Uncertain significance (Jan 12, 2018)
1-183186347-C-A		Junctional epidermolysis bullosa • Junctional epidermolysis bullosa, non-Herlitz type • Junctional epidermolysis bullosa gravis of Herlitz	Benign (Jul 08, 2021)
1-183186353-A-G		Junctional epidermolysis bullosa • Junctional epidermolysis bullosa gravis of Herlitz	Conflicting classifications of pathogenicity (Jan 13, 2018)
1-183186354-T-C			Pathogenic (Mar 28, 2016)
1-183186355-G-T		Junctional epidermolysis bullosa gravis of Herlitz	Likely pathogenic (Jan 11, 2017)
1-183186358-T-C			Likely benign (Mar 03, 2022)
1-183186361-G-C			Likely benign (Aug 16, 2023)
1-183186361-G-T			Likely benign (Jan 29, 2024)
1-183186366-G-A			Likely pathogenic (Dec 21, 2022)
1-183186371-G-A		Inborn genetic diseases	Likely benign (Dec 15, 2023)
1-183186373-C-G			Likely benign (Dec 26, 2023)
1-183186373-C-T			Likely benign (Mar 05, 2022)
1-183186382-C-G			Likely benign (Jul 17, 2023)
1-183186382-C-T			Likely benign (Apr 14, 2022)
1-183186388-C-T			Likely benign (Aug 16, 2023)
1-183186391-G-C			Likely benign (Mar 01, 2023)
1-183186391-G-T			Likely benign (Nov 06, 2023)
1-183186394-C-G			Likely benign (Sep 10, 2023)
1-183186400-G-C			Benign (Dec 30, 2023)
1-183186400-G-T		Junctional epidermolysis bullosa	Conflicting classifications of pathogenicity (Jan 14, 2024)
1-183186403-C-T			Likely benign (May 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMC2	protein_coding	protein_coding	ENST00000264144	23	58663

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.88e-12	1.00	125669	0	79	125748	0.000314

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.346	627	652	0.962	0.0000367	7819
Missense in Polyphen		189	222.92	0.84783		2706
Synonymous	0.611	234	246	0.951	0.0000138	2285
Loss of Function	3.83	30	62.8	0.478	0.00000366	724

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000300	0.000300
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000489	0.000489
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000449	0.000448
Middle Eastern	0.000489	0.000489
South Asian	0.000262	0.000261
Other	0.000163	0.000163

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. Ladsin exerts cell- scattering activity toward a wide variety of cells, including epithelial, endothelial, and fibroblastic cells. {ECO:0000269|PubMed:8265624}.
• Disease: DISEASE: Epidermolysis bullosa, junctional, Herlitz type (H-JEB) [MIM:226700]: An infantile and lethal form of junctional epidermolysis bullosa, a group of blistering skin diseases characterized by tissue separation which occurs within the dermo- epidermal basement In the Herlitz type, death occurs usually within the first six months of life. Occasionally, children survive to teens. It is marked by bullous lesions at birth and extensive denudation of skin and mucous membranes that may be hemorrhagic. {ECO:0000269|PubMed:11810295, ECO:0000269|PubMed:8012393}. 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);Small cell lung cancer - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Alpha 6 Beta 4 signaling pathway;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Inflammatory Response Pathway;Assembly of collagen fibrils and other multimeric structures;Signal Transduction;prion pathway;Alpha6Beta4Integrin;Laminin interactions;Collagen formation;Extracellular matrix organization;Anchoring fibril formation;Integrin;agrin in postsynaptic differentiation;Degradation of the extracellular matrix;a6b1 and a6b4 Integrin signaling;Non-integrin membrane-ECM interactions;MET activates PTK2 signaling;MET promotes cell motility;Signaling by MET;Type I hemidesmosome assembly;Cell junction organization;Signaling by Receptor Tyrosine Kinases;Cell-Cell communication;Beta1 integrin cell surface interactions;Alpha6 beta4 integrin-ligand interactions (Consensus)

Recessive Scores

• pRec: 0.413

Intolerance Scores

• loftool: 0.774
• rvis_EVS: 0.55
• rvis_percentile_EVS: 81.39

Haploinsufficiency Scores

• pHI: 0.0968
• hipred: N
• hipred_score: 0.372
• ghis: 0.448

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.352

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lamc2
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; limbs/digits/tail phenotype; craniofacial 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); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; skeleton phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype

Gene ontology

• Biological process: cell adhesion;positive regulation of cell population proliferation;epidermis development;extracellular matrix organization;positive regulation of cell migration;hemidesmosome assembly;system development;basement membrane assembly
• Cellular component: extracellular region;laminin-2 complex;extracellular space;cell cortex;membrane;perinuclear region of cytoplasm;collagen-containing extracellular matrix
• Molecular function: extracellular matrix structural constituent;heparin binding