EPS8L2

EPS8 like 2

Basic information

Region (hg38): 11:694437-727727

Links

ENSG00000177106 ∙ NCBI:64787 ∙ OMIM:614988 ∙ HGNC:21296 ∙ Uniprot:Q9H6S3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive 106 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive 106 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 106	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	26282398
Prelingual hearing loss has been described in some (but not all) individuals

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EPS8L2 gene.

• not provided (4 variants)
• Hearing loss, autosomal recessive 106 (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EPS8L2 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	48	4	54
missense			125	6	2	133
nonsense	1	1	1			3
start loss						0
frameshift	4				1	5
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region			1	15	2	18
non coding			3	34	26	63
Total	5	1	134	88	33

Highest pathogenic variant AF is 0.000251

Variants in EPS8L2

This is a list of pathogenic ClinVar variants found in the EPS8L2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-694743-C-T			Likely benign (Mar 18, 2022)
11-694746-C-T			Likely benign (Sep 04, 2021)
11-694747-G-A			Likely benign (Jan 15, 2024)
11-694750-C-T			Likely benign (Sep 16, 2022)
11-694751-G-A			Likely benign (Oct 08, 2022)
11-694756-T-G			Uncertain significance (Apr 18, 2022)
11-694759-C-T			Uncertain significance (Oct 22, 2023)
11-694768-C-T		Inborn genetic diseases	Uncertain significance (May 29, 2023)
11-694771-C-T			Uncertain significance (Oct 28, 2022)
11-694777-C-T			Uncertain significance (Dec 11, 2023)
11-694781-G-A			Likely benign (Aug 17, 2023)
11-694780-C-CGGCCTCGTCGGGGCCGGGCAG			Uncertain significance (Jul 12, 2022)
11-694789-C-T			Uncertain significance (Aug 24, 2023)
11-694793-G-A			Likely benign (Nov 01, 2021)
11-694794-C-A			Uncertain significance (Aug 12, 2022)
11-694795-C-G			Uncertain significance (Jan 22, 2024)
11-694796-G-A			Likely benign (Jun 24, 2021)
11-694797-G-C			Uncertain significance (Dec 01, 2023)
11-694804-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 30, 2023)
11-694808-G-A			Likely benign (Jan 14, 2024)
11-694811-G-A			Likely benign (Oct 01, 2022)
11-694816-T-C			Likely benign (Jan 11, 2024)
11-694817-G-A		not specified	Benign/Likely benign (Feb 01, 2024)
11-694822-T-C			Uncertain significance (May 10, 2022)
11-694827-C-T			Uncertain significance (Aug 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EPS8L2	protein_coding	protein_coding	ENST00000533256	20	33290

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000149	1.00	125560	0	107	125667	0.000426

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.799	451	406	1.11	0.0000242	4584
Missense in Polyphen		139	130.46	1.0654		1546
Synonymous	-1.94	214	181	1.18	0.0000118	1355
Loss of Function	3.44	17	40.6	0.418	0.00000199	454

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00139	0.00131
Ashkenazi Jewish	0.000110	0.0000993
East Asian	0.000478	0.000435
Finnish	0.000288	0.000277
European (Non-Finnish)	0.000495	0.000466
Middle Eastern	0.000478	0.000435
South Asian	0.000339	0.000327
Other	0.000524	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stimulates guanine exchange activity of SOS1. May play a role in membrane ruffling and remodeling of the actin cytoskeleton. In the cochlea, is required for stereocilia maintenance in adult hair cells (By similarity). {ECO:0000250|UniProtKB:Q99K30, ECO:0000269|PubMed:14565974}.

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.602
• rvis_EVS: -1.26
• rvis_percentile_EVS: 5.28

Haploinsufficiency Scores

• pHI: 0.209
• hipred: N
• hipred_score: 0.384
• ghis: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.749

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Eps8l2
• 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)

Gene ontology

• Biological process: Rho protein signal transduction;sensory perception of sound;regulation of Rho protein signal transduction;positive regulation of ruffle assembly
• Cellular component: cytosol;plasma membrane;vesicle;stereocilium bundle;stereocilium tip;ruffle membrane;protein-containing complex;extracellular exosome
• Molecular function: actin binding;Rho guanyl-nucleotide exchange factor activity;protein binding;Rac guanyl-nucleotide exchange factor activity;cadherin binding