DIAPH2

diaphanous related formin 2, the group of Formins|Armadillo like helical domain containing

Basic information

Region (hg38): X:96684711-97604997

Links

ENSG00000147202 ∙ NCBI:1730 ∙ OMIM:300108 ∙ HGNC:2877 ∙ Uniprot:O60879 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• premature ovarian failure 2A (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Premature ovarian failure 2A	XL	Obstetric	Genetic knowledge may allow steps to enable fertility preservation	Endocrine; Obstetric	8406446; 9070928; 9497258
Reported individuals have been affected with cytogenetic imbalances

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DIAPH2 gene.

• Inborn genetic diseases (31 variants)
• not provided (17 variants)
• Premature ovarian failure 2A (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DIAPH2 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				8	2	10
missense			16	3		19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding			13	3	1	17
Total	0	0	29	14	3

Variants in DIAPH2

This is a list of pathogenic ClinVar variants found in the DIAPH2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-96685074-G-A		not specified	Uncertain significance (Jul 20, 2022)
X-96738667-G-A		Premature ovarian failure 2A	Benign/Likely benign (Dec 31, 2019)
X-96738669-G-A			Likely benign (Nov 15, 2017)
X-96738710-G-C		not specified	Uncertain significance (Nov 07, 2023)
X-96758171-C-T			Likely benign (Mar 01, 2022)
X-96758210-C-T		DIAPH2-related disorder	Likely benign (Mar 05, 2019)
X-96881646-C-T			Likely benign (Mar 01, 2023)
X-96881692-G-A			Likely benign (May 29, 2018)
X-96881726-G-A			Likely benign (Mar 01, 2022)
X-96884323-G-A			Likely benign (Mar 01, 2023)
X-96884336-A-G		not specified	Uncertain significance (Dec 27, 2022)
X-96884354-C-A		not specified	Uncertain significance (Jun 27, 2023)
X-96884398-G-C		not specified	Uncertain significance (Sep 16, 2021)
X-96884410-A-G		not specified	Likely benign (Mar 12, 2024)
X-96884512-G-A		not specified	Uncertain significance (Jul 05, 2022)
X-96884635-G-C		not specified	Uncertain significance (Aug 09, 2021)
X-96884682-T-C			Likely benign (Oct 01, 2022)
X-96884701-C-G		not specified	Uncertain significance (Jul 12, 2023)
X-96884828-G-A		not specified	Uncertain significance (Mar 29, 2022)
X-96884851-C-A		not specified	Uncertain significance (Jan 09, 2024)
X-96884878-G-T		not specified	Conflicting classifications of pathogenicity (Feb 01, 2024)
X-96884902-C-T		not specified	Uncertain significance (Dec 17, 2023)
X-96884903-G-A		not specified	Uncertain significance (Feb 03, 2022)
X-96884903-G-T		not specified	Likely benign (Aug 22, 2023)
X-96884959-G-A		not specified	Uncertain significance (Jun 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DIAPH2	protein_coding	protein_coding	ENST00000324765	27	920335

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00557	125661	3	5	125669	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.83	261	359	0.728	0.0000265	7252
Missense in Polyphen		54	96.589	0.55907		2022
Synonymous	-1.33	142	123	1.15	0.00000924	1991
Loss of Function	5.14	6	41.9	0.143	0.00000358	787

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000366	0.0000366
Ashkenazi Jewish	0.000143	0.0000993
East Asian	0.0000767	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000525	0.0000352
Middle Eastern	0.0000767	0.0000544
South Asian	0.0000598	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Could be involved in oogenesis. Involved in the regulation of endosome dynamics. Implicated in a novel signal transduction pathway, in which isoform 3 and CSK are sequentially activated by RHOD to regulate the motility of early endosomes through interactions with the actin cytoskeleton. {ECO:0000269|PubMed:12577064}.
• Disease: DISEASE: Premature ovarian failure 2A (POF2A) [MIM:300511]: An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol. {ECO:0000269|PubMed:9497258}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Regulation of actin cytoskeleton - Homo sapiens (human);Signal Transduction;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases (Consensus)

Recessive Scores

• pRec: 0.273

Intolerance Scores

• loftool: 0.222
• rvis_EVS: -1
• rvis_percentile_EVS: 8.37

Haploinsufficiency Scores

• pHI: 0.569
• hipred: Y
• hipred_score: 0.608
• ghis: 0.586

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.617

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Diaph2
• 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: diaph2
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: actin filament organization;multicellular organism development;female gamete generation;oogenesis
• Cellular component: nucleolus;early endosome;endoplasmic reticulum;cytosol;intracellular membrane-bounded organelle
• Molecular function: actin binding;signaling receptor binding;Rho GTPase binding