LRIG2

leucine rich repeats and immunoglobulin like domains 2, the group of I-set domain containing

Basic information

Region (hg38): 1:113073197-113132260

Links

ENSG00000198799 ∙ NCBI:9860 ∙ OMIM:608869 ∙ HGNC:20889 ∙ Uniprot:O94898 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• urofacial syndrome type 1 (Strong), mode of inheritance: AR
• urofacial syndrome 2 (Strong), mode of inheritance: AR
• Ochoa syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Urofacial syndrome 2	AR	Renal	Individuals have been described with manifestations including low-capacity, overactive bladder, vesicoureteral reflux, hydronephrosis, urosepsis, and renal impairment, though treatment attempts (eg, with intermittent catheterization, antimuscarinic agents, and surgical bladder augmentation) were not reported as slowing slow renal failure, and dialysis was required in at least one individual; Early recognition may allow management aimed at preserving renal function	Craniofacial; Renal	23313374
Wilms tumor has been reported in one individual

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LRIG2 gene.

• Global developmental delay (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LRIG2 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				11	1	12
missense			52	8	4	64
nonsense						0
start loss						0
frameshift	1	1				2
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region				3		3
non coding					2	2
Total	2	2	52	19	7

Highest pathogenic variant AF is 0.0000131

Variants in LRIG2

This is a list of pathogenic ClinVar variants found in the LRIG2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-113073409-G-A			Uncertain significance (Sep 16, 2018)
1-113073412-G-C			Likely benign (Dec 31, 2019)
1-113073422-CT-C			Pathogenic (Nov 19, 2017)
1-113073426-G-C		LRIG2-related disorder • not specified	Conflicting classifications of pathogenicity (Feb 03, 2022)
1-113073474-G-A		not specified	Uncertain significance (Feb 27, 2023)
1-113073500-C-G		not specified	Uncertain significance (May 10, 2024)
1-113073521-G-A		not specified	Likely benign (May 27, 2022)
1-113073541-G-A			Likely benign (Feb 20, 2018)
1-113073549-C-T		not specified	Uncertain significance (Mar 24, 2023)
1-113073557-A-G		not specified	Uncertain significance (Dec 22, 2023)
1-113073626-C-A		not specified	Uncertain significance (Feb 17, 2024)
1-113091334-C-T		Urofacial syndrome 2	Uncertain significance (Mar 05, 2018)
1-113091370-A-T		not specified	Uncertain significance (Jun 22, 2023)
1-113093204-A-G			Likely pathogenic (Sep 14, 2017)
1-113093431-G-A		not specified	Uncertain significance (Jan 03, 2024)
1-113093435-A-G		not specified	Uncertain significance (Dec 26, 2023)
1-113093512-A-T			Likely benign (Dec 31, 2019)
1-113093546-G-A		not specified	Likely benign (Jul 08, 2022)
1-113093555-T-C		not specified	Uncertain significance (Nov 15, 2021)
1-113094365-C-T		not specified	Likely benign (Jun 29, 2023)
1-113094384-C-T		LRIG2-related disorder	Likely benign (Jul 03, 2019)
1-113094433-A-G		not specified	Uncertain significance (Oct 13, 2023)
1-113094605-G-A		LRIG2-related disorder	Likely benign (Aug 01, 2019)
1-113094672-C-G			Likely benign (Oct 19, 2018)
1-113094686-A-G		not specified	Uncertain significance (Dec 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LRIG2	protein_coding	protein_coding	ENST00000361127	18	59052

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.97e-18	0.798	125617	1	130	125748	0.000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.482	542	575	0.943	0.0000292	7001
Missense in Polyphen		98	122.51	0.79993		1563
Synonymous	-0.0610	215	214	1.01	0.0000108	2057
Loss of Function	2.10	35	51.2	0.683	0.00000279	598

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000842	0.000842
Ashkenazi Jewish	0.00	0.00
East Asian	0.000871	0.000870
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000703	0.000695
Middle Eastern	0.000871	0.000870
South Asian	0.000460	0.000425
Other	0.000175	0.000163

dbNSFP

Source: dbNSFP

Recessive Scores

• pRec: 0.0859

Intolerance Scores

• loftool: 0.938
• rvis_EVS: -0.35
• rvis_percentile_EVS: 29.59

Haploinsufficiency Scores

• pHI: 0.132
• hipred: N
• hipred_score: 0.237
• ghis: 0.541

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.168

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lrig2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; 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); 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; 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); growth/size/body region phenotype

Gene ontology

• Biological process: sensory perception of sound;regulation of platelet-derived growth factor receptor signaling pathway;negative regulation of axon regeneration;negative regulation of membrane protein ectodomain proteolysis;innervation;positive regulation of protein localization to cell surface;regulation of neuron migration
• Cellular component: extracellular space;cytoplasm;plasma membrane;integral component of membrane;growth cone;extracellular matrix;neuronal cell body;intracellular vesicle
• Molecular function: signaling receptor binding