YTHDC2

YTH N6-methyladenosine RNA binding protein C2, the group of YTH domain containing N6-methyladenosine readers

Basic information

Region (hg38): 5:113513693-113595285

Links

ENSG00000047188 ∙ NCBI:64848 ∙ OMIM:616530 ∙ HGNC:24721 ∙ Uniprot:Q9H6S0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the YTHDC2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YTHDC2 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				7	13	20
missense			58	8	8	74
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				8	4	12
non coding				2	3	5
Total	0	0	58	17	24

Variants in YTHDC2

This is a list of pathogenic ClinVar variants found in the YTHDC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-113513890-A-G		YTHDC2-related disorder	Likely benign (Apr 05, 2019)
5-113513930-C-T		YTHDC2-related disorder	Benign (Dec 31, 2019)
5-113513942-G-T		not specified	Uncertain significance (Jan 30, 2024)
5-113515266-G-A		YTHDC2-related disorder	Benign (Oct 30, 2019)
5-113525124-G-A		not specified	Uncertain significance (Aug 17, 2022)
5-113525168-G-A		not specified	Uncertain significance (Dec 07, 2021)
5-113526601-G-A		not specified	Uncertain significance (Jun 29, 2022)
5-113526616-G-A		not specified	Uncertain significance (Jan 23, 2024)
5-113526634-C-T		not specified	Uncertain significance (Jan 30, 2024)
5-113526661-C-A		not specified	Uncertain significance (Nov 14, 2023)
5-113526744-G-C		not specified	Uncertain significance (Feb 14, 2023)
5-113526745-T-C		not specified	Uncertain significance (Sep 23, 2023)
5-113526754-T-C		not specified	Uncertain significance (Feb 16, 2023)
5-113532871-T-C		YTHDC2-related disorder	Likely benign (Apr 05, 2019)
5-113532916-G-A		not specified	Uncertain significance (May 21, 2024)
5-113532933-T-G		not specified	Uncertain significance (Jun 27, 2022)
5-113532986-C-T		YTHDC2-related disorder	Likely benign (Mar 28, 2019)
5-113532996-C-A		YTHDC2-related disorder	Benign (Oct 18, 2019)
5-113532997-G-A		YTHDC2-related disorder	Likely benign (Oct 27, 2022)
5-113534379-C-T		not specified	Uncertain significance (May 27, 2022)
5-113534385-C-T		not specified	Uncertain significance (May 10, 2022)
5-113534404-C-T		YTHDC2-related disorder	Benign (Dec 31, 2019)
5-113535638-A-G			Likely benign (May 08, 2018)
5-113535666-T-C		YTHDC2-related disorder	Likely benign (May 22, 2023)
5-113535668-T-C		YTHDC2-related disorder	Benign (Feb 26, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YTHDC2	protein_coding	protein_coding	ENST00000161863	29	81603

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	6.56e-10	125731	0	16	125747	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.325	712	737	0.966	0.0000370	9361
Missense in Polyphen		122	180.01	0.67775		2360
Synonymous	-2.27	291	246	1.18	0.0000117	2728
Loss of Function	7.78	5	80.1	0.0624	0.00000494	905

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000584	0.0000584
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000971	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000340	0.0000327
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 3'-5' RNA helicase that plays a key role in the male and female germline by promoting transition from mitotic to meiotic divisions in stem cells (PubMed:26318451, PubMed:29033321). Specifically recognizes and binds N6-methyladenosine (m6A)- containing RNAs, a modification present at internal sites of mRNAs and some non-coding RNAs that plays a role in the efficiency of RNA processing and stability (PubMed:26318451, PubMed:29033321). Essential for ensuring a successful progression of the meiotic program in the germline by regulating the level of m6A-containing RNAs (By similarity). Acts by binding and promoting degradation of m6A-containing mRNAs: the 3'-5' RNA helicase activity is required for this process and RNA degradation may be mediated by XRN1 exoribonuclease (PubMed:29033321). Required for both spermatogenesis and oogenesis (By similarity). {ECO:0000250|UniProtKB:B2RR83, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:29033321}.

Recessive Scores

• pRec: 0.0970

Intolerance Scores

• loftool: 0.400
• rvis_EVS: -0.28
• rvis_percentile_EVS: 33.59

Haploinsufficiency Scores

• pHI: 0.414
• hipred: N
• hipred_score: 0.414
• ghis: 0.612

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.829

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ythdc2
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype

Gene ontology

• Biological process: spermatid development;response to tumor necrosis factor;positive regulation by host of viral genome replication;oocyte development;meiotic cell cycle;germline cell cycle switching, mitotic to meiotic cell cycle;response to interleukin-1
• Cellular component: nucleus;cytoplasm;endoplasmic reticulum;ribonucleoprotein granule
• Molecular function: RNA binding;protein binding;ATP binding;RNA-dependent ATPase activity;3'-5' RNA helicase activity;ATP-dependent 3'-5' RNA helicase activity;RNA polymerase binding;N6-methyladenosine-containing RNA binding