STAG2

stromal antigen 2, the group of Cohesin complex|Armadillo like helical domain containing

Basic information

Region (hg38): X:123960212-124422664

Links

ENSG00000101972 ∙ NCBI:10735 ∙ OMIM:300826 ∙ HGNC:11355 ∙ Uniprot:Q8N3U4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Mullegama-Klein-Martinez syndrome (Strong), mode of inheritance: XL
• Mullegama-Klein-Martinez syndrome (Strong), mode of inheritance: XL
• Mullegama-Klein-Martinez syndrome (Strong), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mullegama-Klein-Martinez syndrome (Neurodevelopmental disorder, X-linked, with craniofacial abnormalities); Holoprosencephaly 13, X-linked	XL	Cardiovascular	The conditions can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	28296084; 29263825; 30158690; 30447054; 30765867; 31334757

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STAG2 gene.

• not provided (5 variants)
• Mullegama-Klein-Martinez syndrome (3 variants)
• Holoprosencephaly 13, X-linked (3 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STAG2 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			5	99	18	122
missense		5	165	5	9	184
nonsense	2	3				5
start loss						0
frameshift	6	2				8
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	2	4	2	2	12
splice region		1	19	41	18	79
non coding			5	82	35	122
Total	10	12	180	188	64

Variants in STAG2

This is a list of pathogenic ClinVar variants found in the STAG2 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-124022370-CA-C			Benign (May 17, 2021)
X-124022528-A-G			Uncertain significance (Nov 11, 2022)
X-124022632-T-C		Mullegama-Klein-Martinez syndrome	Uncertain significance (Sep 19, 2020)
X-124022649-C-A		Mullegama-Klein-Martinez syndrome;Holoprosencephaly 13, X-linked	Conflicting classifications of pathogenicity (Sep 20, 2024)
X-124022662-A-G			Uncertain significance (Nov 10, 2023)
X-124022668-T-A			Uncertain significance (Nov 13, 2023)
X-124022678-A-G			Likely benign (Feb 21, 2023)
X-124022681-T-A			Likely benign (Jan 17, 2023)
X-124025683-A-G			Benign (May 17, 2021)
X-124025825-A-C			Likely benign (Oct 02, 2022)
X-124025829-T-C		Mullegama-Klein-Martinez syndrome;Holoprosencephaly 13, X-linked	Benign/Likely benign (Jan 26, 2024)
X-124025861-T-C			Likely benign (Oct 10, 2023)
X-124025885-C-T			Likely benign (Jul 15, 2022)
X-124025893-A-G		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
X-124025922-T-C			Benign (Jan 06, 2024)
X-124025929-A-C			Likely benign (Oct 04, 2022)
X-124025931-T-C			Likely benign (Aug 22, 2022)
X-124025936-G-A			Likely benign (Dec 28, 2023)
X-124030945-C-T			Benign (Dec 13, 2023)
X-124030946-G-A			Likely benign (Aug 10, 2023)
X-124030948-A-G			Likely benign (Oct 13, 2021)
X-124030948-A-AT			Benign (Sep 09, 2023)
X-124030980-A-G			Uncertain significance (Aug 19, 2022)
X-124030982-G-T			Uncertain significance (Jan 07, 2022)
X-124030986-C-T			Uncertain significance (Sep 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STAG2	protein_coding	protein_coding	ENST00000218089	33	462453

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.42e-8	121668	0	1	121669	0.00000411

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.94	151	444	0.340	0.0000324	8460
Missense in Polyphen		20	132.2	0.15128		2573
Synonymous	-0.369	146	140	1.04	0.00000971	2208
Loss of Function	6.61	1	52.8	0.0189	0.00000432	926

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000629	0.0000467
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis. {ECO:0000269|PubMed:12034751}.
• Pathway: Cell cycle - Homo sapiens (human);Signal Transduction;SUMOylation of DNA damage response and repair proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Reproduction;SUMOylation;Establishment of Sister Chromatid Cohesion;S Phase;Meiotic synapsis;Meiosis;Signaling by Nuclear Receptors;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;Cohesin Loading onto Chromatin;Mitotic Telophase/Cytokinesis;M Phase;Estrogen-dependent gene expression;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;ESR-mediated signaling;PLK1 signaling events (Consensus)

Intolerance Scores

• rvis_EVS: -0.63
• rvis_percentile_EVS: 17.03

Haploinsufficiency Scores

• pHI: 0.703
• hipred: Y
• hipred_score: 0.859
• ghis: 0.651

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.894

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Stag2

Gene ontology

• Biological process: sister chromatid cohesion;negative regulation of DNA endoreduplication;cell division;meiotic cell cycle;regulation of mitotic spindle assembly
• Cellular component: chromosome, centromeric region;chromatin;nucleus;nucleoplasm;chromosome;cytosol;cohesin complex;membrane;nuclear matrix;mitotic spindle pole
• Molecular function: chromatin binding;protein binding