ERCC6L2

ERCC excision repair 6 like 2

Basic information

Region (hg38): 9:95871263-96121154

Previous symbols: [ "C9orf102" ]

Links

ENSG00000182150 ∙ NCBI:375748 ∙ OMIM:615667 ∙ HGNC:26922 ∙ Uniprot:Q5T890 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pancytopenia-developmental delay syndrome (Definitive), mode of inheritance: AR
• pancytopenia-developmental delay syndrome (Supportive), mode of inheritance: AR
• pancytopenia-developmental delay syndrome (Definitive), mode of inheritance: AR
• pancytopenia-developmental delay syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bone marrow failure syndrome 2	AR	Hematologic	Individuals have been described with tri-lineage bone marrow failure, and awareness may allow prompt recognition and management related to hematologic (eg, anemia) and infectious sequelae	Hematologic; Neurologic	24507776

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ERCC6L2 gene.

• not provided (611 variants)
• not specified (31 variants)
• Inborn genetic diseases (23 variants)
• Pancytopenia-developmental delay syndrome (17 variants)
• ERCC6L2-related condition (6 variants)
• Bone marrow hypocellularity (2 variants)
• Thrombocytopenia (1 variants)
• Bone marrow hypocellularity;Pancytopenia (1 variants)
• Hereditary cancer-predisposing syndrome (1 variants)
• Premature ovarian insufficiency (1 variants)
• - (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ERCC6L2 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				132	8	140
missense			312	10	15	337
nonsense	4	1				5
start loss						0
frameshift	8	7	3			18
inframe indel			7			7
splice donor/acceptor (+/-2bp)		4				4
splice region			10	16	2	28
non coding			11	62	14	87
Total	12	12	333	204	37

Highest pathogenic variant AF is 0.000204

Variants in ERCC6L2

This is a list of pathogenic ClinVar variants found in the ERCC6L2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-95876006-A-G			Benign (Feb 01, 2024)
9-95876007-T-G			Uncertain significance (May 23, 2023)
9-95876009-C-G			Uncertain significance (Apr 06, 2023)
9-95876013-C-T			Uncertain significance (Oct 24, 2021)
9-95876015-G-C			Uncertain significance (Dec 17, 2020)
9-95876023-C-T			Likely benign (Aug 19, 2022)
9-95876024-C-T			Benign (Feb 01, 2024)
9-95876026-T-A		ERCC6L2-related disorder	Benign/Likely benign (Feb 09, 2024)
9-95876026-TC-AA			Benign (Jan 19, 2024)
9-95876027-C-A		ERCC6L2-related disorder	Benign/Likely benign (Feb 09, 2024)
9-95876027-C-T		Inborn genetic diseases	Uncertain significance (Feb 16, 2023)
9-95876029-C-T			Likely benign (Mar 14, 2022)
9-95876030-C-G			Uncertain significance (Mar 16, 2022)
9-95876031-C-G		not specified	Benign (Jan 16, 2024)
9-95876038-G-C			Likely benign (Jan 04, 2024)
9-95876038-G-T			Benign (Mar 14, 2023)
9-95876042-G-A		Inborn genetic diseases	Uncertain significance (Nov 12, 2023)
9-95876043-A-G			Uncertain significance (May 16, 2021)
9-95876046-C-A		not specified • ERCC6L2-related disorder	Benign/Likely benign (Mar 01, 2024)
9-95876046-C-T			Uncertain significance (Sep 01, 2021)
9-95876047-G-T			Likely benign (Nov 02, 2023)
9-95876051-G-C			Uncertain significance (Aug 28, 2023)
9-95876053-G-C			Likely benign (Feb 22, 2023)
9-95876054-C-T			Uncertain significance (Jan 15, 2024)
9-95876055-C-A			Uncertain significance (Oct 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ERCC6L2	protein_coding	protein_coding	ENST00000288985	14	138860

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.06e-7	1.00	125564	1	183	125748	0.000732

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.636	334	368	0.907	0.0000182	4661
Missense in Polyphen		86	137.19	0.62689		1719
Synonymous	-0.849	141	129	1.10	0.00000634	1344
Loss of Function	3.13	17	37.7	0.450	0.00000215	458

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000334	0.000334
Ashkenazi Jewish	0.00	0.00
East Asian	0.000396	0.000381
Finnish	0.00525	0.00519
European (Non-Finnish)	0.000457	0.000440
Middle Eastern	0.000396	0.000381
South Asian	0.0000983	0.0000980
Other	0.000494	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in early DNA damage response. {ECO:0000269|PubMed:24507776}.
• Disease: DISEASE: Bone marrow failure syndrome 2 (BMFS2) [MIM:615715]: An autosomal recessive disorder characterized by trilineage bone marrow failure, bone marrow hypocellularity, learning difficulties, and microcephaly. Insufficient hematopoiesis results in peripheral blood cytopenias, affecting myeloid, erythroid and megakaryocyte lines. Cutaneous features and increased chromosome breakage are not features. {ECO:0000269|PubMed:24507776}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0840

Haploinsufficiency Scores

• pHI: 0.0622
• hipred: N
• hipred_score: 0.379
• ghis: 0.458

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ercc6l2

Gene ontology

• Biological process: cellular response to reactive oxygen species;interstrand cross-link repair
• Cellular component: nucleus;cytoplasm;mitochondrion;centrosome;protein-containing complex
• Molecular function: DNA binding;helicase activity;ATP binding;protein kinase binding