CLRN2

clarin 2, the group of Clarins

Basic information

Region (hg38): 4:17515164-17527104

Links

ENSG00000249581 ∙ NCBI:645104 ∙ OMIM:618988 ∙ HGNC:33939 ∙ Uniprot:A0PK11 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal recessive 117 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 117	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	33496845

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CLRN2 gene.

• Inborn genetic diseases (9 variants)
• not provided (2 variants)
• CLRN2-related condition (1 variants)
• Hearing loss, autosomal recessive 117 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CLRN2 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						0
missense			10	1	1	12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	10	1	1

Variants in CLRN2

This is a list of pathogenic ClinVar variants found in the CLRN2 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-17515274-G-T		not specified	Uncertain significance (Dec 08, 2023)
4-17515287-G-C		not specified	Uncertain significance (Jan 30, 2024)
4-17515327-T-G		not specified	Uncertain significance (Dec 19, 2023)
4-17515342-G-A		not specified	Uncertain significance (Oct 10, 2023)
4-17515466-G-A		not specified	Uncertain significance (Feb 06, 2023)
4-17515472-G-A		CLRN2-related disorder • not specified	Uncertain significance (Jul 19, 2023)
4-17515501-C-T		CLRN2-related disorder	Uncertain significance (Jan 03, 2024)
4-17515502-G-T		Hearing loss, autosomal recessive 117	Uncertain significance (Jan 03, 2022)
4-17522947-C-G			Benign (Apr 27, 2020)
4-17523007-G-C		not specified	Uncertain significance (Nov 08, 2022)
4-17523040-G-A		not specified	Uncertain significance (Jan 11, 2023)
4-17526856-C-T		not specified	Uncertain significance (Sep 16, 2021)
4-17526877-C-A		Hearing loss, autosomal recessive 117	Pathogenic (Apr 08, 2024)
4-17526916-T-C		not specified	Uncertain significance (May 25, 2022)
4-17526930-G-A		not specified	Uncertain significance (Dec 28, 2023)
4-17526960-G-A		not specified	Uncertain significance (May 18, 2022)
4-17526973-C-T			Likely benign (Oct 01, 2022)
4-17526979-A-T		CLRN2-related disorder	Likely benign (Nov 28, 2023)
4-17526996-G-T		not specified	Uncertain significance (Jan 17, 2023)
4-17527032-A-C		not specified	Uncertain significance (Oct 16, 2023)
4-17527054-C-T		not specified	Uncertain significance (Oct 12, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CLRN2	protein_coding	protein_coding	ENST00000511148	3	11940

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000202	0.278	124627	0	35	124662	0.000140

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.263	136	145	0.939	0.00000907	1500
Missense in Polyphen		56	55.432	1.0102		577
Synonymous	-0.767	74	66.1	1.12	0.00000483	486
Loss of Function	0.178	9	9.60	0.938	5.95e-7	87

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000468	0.000467
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000111
Finnish	0.000186	0.000186
European (Non-Finnish)	0.000143	0.000142
Middle Eastern	0.000111	0.000111
South Asian	0.0000327	0.0000327
Other	0.000331	0.000330

dbNSFP

Source: dbNSFP

Recessive Scores

• pRec: 0.102

Intolerance Scores

• loftool: 0.528
• rvis_EVS: -0.14
• rvis_percentile_EVS: 43.57

Haploinsufficiency Scores

• pHI: 0.141
• hipred: N
• hipred_score: 0.251
• ghis: 0.409

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0953

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Clrn2

Gene ontology

• Cellular component: integral component of membrane