APC2

APC regulator of WNT signaling pathway 2, the group of Armadillo repeat containing

Basic information

Region (hg38): 19:1446302-1473244

Links

ENSG00000115266 ∙ NCBI:10297 ∙ OMIM:612034 ∙ HGNC:24036 ∙ Uniprot:O95996 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cortical dysplasia, complex, with other brain malformations 10 (Moderate), mode of inheritance: AR
• cortical dysplasia, complex, with other brain malformations 10 (Strong), mode of inheritance: AR
• Sotos syndrome (Supportive), mode of inheritance: AD
• cortical dysplasia, complex, with other brain malformations 10 (Strong), mode of inheritance: AR
• intellectual developmental disorder, autosomal recessive 74 (Limited), mode of inheritance: Unknown
• lissencephaly spectrum disorders (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 74 (Sotos syndrome 3); Cortical dysplasia, complex, with other brain malformations 10	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	25753423; 31585108

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the APC2 gene.

• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the APC2 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			4	257	25	286
missense			402	19	12	433
nonsense		1				1
start loss						0
frameshift	2	2	2			6
inframe indel			9	1		10
splice donor/acceptor (+/-2bp)		1				1
splice region			6	10	1	17
non coding			1	38	9	48
Total	2	4	418	315	46

Variants in APC2

This is a list of pathogenic ClinVar variants found in the APC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-1450086-C-T			Likely benign (Apr 01, 2023)
19-1453013-C-T			Likely benign (Apr 01, 2023)
19-1453018-C-T		APC2-related disorder	Likely benign (Jan 29, 2024)
19-1453019-G-A			Likely benign (Feb 21, 2022)
19-1453025-C-T			Likely benign (Mar 29, 2018)
19-1453064-G-C			Uncertain significance (Sep 01, 2022)
19-1453093-A-C		Inborn genetic diseases	Uncertain significance (Mar 29, 2022)
19-1453094-C-G		not specified	Uncertain significance (Oct 17, 2023)
19-1453130-G-A			Likely benign (Aug 02, 2023)
19-1453133-G-A		APC2-related disorder	Likely benign (Aug 06, 2023)
19-1453135-G-C		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
19-1453161-G-A			Benign (Feb 01, 2024)
19-1453227-C-T			Likely benign (Feb 10, 2022)
19-1453236-C-T			Likely benign (Nov 29, 2023)
19-1453270-A-G			Likely benign (Jun 20, 2018)
19-1453290-G-A			Uncertain significance (Nov 01, 2022)
19-1453290-G-C		Inborn genetic diseases	Uncertain significance (Jan 12, 2024)
19-1453305-C-T		Inborn genetic diseases	Uncertain significance (Oct 20, 2023)
19-1453307-G-A			Uncertain significance (May 27, 2022)
19-1453309-G-A			Benign (Jan 12, 2024)
19-1453314-C-T		APC2-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 15, 2024)
19-1453315-G-A			Likely benign (Jan 18, 2018)
19-1453343-C-T			Benign (Oct 03, 2023)
19-1453344-G-C			Likely benign (Sep 17, 2017)
19-1453355-C-A			Likely benign (Mar 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
APC2	protein_coding	protein_coding	ENST00000535453	14	26944

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000587	125471	0	15	125486	0.0000598

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.754	1015	1.08e+3	0.936	0.0000664	14009
Missense in Polyphen		280	405.78	0.69003		5077
Synonymous	-2.43	583	513	1.14	0.0000345	5159
Loss of Function	6.24	7	58.5	0.120	0.00000290	702

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000142	0.000126
Ashkenazi Jewish	0.00	0.00
East Asian	0.000120	0.000109
Finnish	0.000101	0.0000924
European (Non-Finnish)	0.0000583	0.0000529
Middle Eastern	0.000120	0.000109
South Asian	0.0000678	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Stabilizes microtubules and may regulate actin fiber dynamics through the activation of Rho family GTPases (PubMed:25753423). May also function in Wnt signaling by promoting the rapid degradation of CTNNB1 (PubMed:10021369, PubMed:11691822, PubMed:9823329). {ECO:0000269|PubMed:10021369, ECO:0000269|PubMed:11691822, ECO:0000269|PubMed:25753423, ECO:0000269|PubMed:9823329}.
• Disease: DISEASE: Sotos syndrome 3 (SOTOS3) [MIM:617169]: A form of Sotos syndrome, a childhood overgrowth syndrome characterized by prenatal and postnatal overgrowth, developmental delay, mental retardation, advanced bone age, and abnormal craniofacial morphology. SOTOS3 patients do not have advanced bone age, hypotonia, seizures, or autism. SOTOS3 transmission pattern is consistent with autosomal recessive inheritance. {ECO:0000269|PubMed:25753423}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gastric cancer - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Breast cancer - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);WNT-Core;Endometrial cancer;Chromosomal and microsatellite instability in colorectal cancer;Regulation of Actin Cytoskeleton (Consensus)

Recessive Scores

• pRec: 0.142

Haploinsufficiency Scores

• pHI: 0.477
• hipred: Y
• hipred_score: 0.857
• ghis: 0.650

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.991

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Apc2
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; reproductive system phenotype; cellular phenotype

Gene ontology

• Biological process: microtubule cytoskeleton organization;cell fate specification;negative regulation of microtubule depolymerization;pattern specification process;Wnt signaling pathway;cell migration;regulation of cell differentiation;positive regulation of protein catabolic process;negative regulation of canonical Wnt signaling pathway;activation of GTPase activity
• Cellular component: cytoplasm;Golgi apparatus;cytosol;cytoplasmic microtubule;actin filament;microtubule cytoskeleton;catenin complex;midbody;beta-catenin destruction complex;lamellipodium membrane;filamentous actin;intercellular bridge;perinuclear region of cytoplasm;postsynapse
• Molecular function: protein binding;beta-catenin binding;microtubule binding;gamma-catenin binding