DAAM2

dishevelled associated activator of morphogenesis 2, the group of Formins|Armadillo like helical domain containing

Basic information

Region (hg38): 6:39792297-39904877

Links

ENSG00000146122 ∙ NCBI:23500 ∙ OMIM:606627 ∙ HGNC:18143 ∙ Uniprot:Q86T65 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephrotic syndrome, type 24 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephrotic syndrome, type 24	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	Renal	33232676
Steroid treatment has been described as ineffective

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DAAM2 gene.

• Inborn genetic diseases (60 variants)
• Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A (18 variants)
• not provided (7 variants)
• Combined molybdoflavoprotein enzyme deficiency (5 variants)
• Nephrotic syndrome, type 24 (5 variants)
• DAAM2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DAAM2 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				1		1
missense	1		64	1	2	68
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding			15	4	5	24
Total	1	0	79	6	7

Highest pathogenic variant AF is 0.000598

Variants in DAAM2

This is a list of pathogenic ClinVar variants found in the DAAM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-39856313-G-A		DAAM2-related disorder	Uncertain significance (Jan 26, 2024)
6-39856313-G-T		Inborn genetic diseases	Uncertain significance (Jul 19, 2023)
6-39856322-G-A		Inborn genetic diseases	Uncertain significance (Oct 25, 2023)
6-39856329-T-C		DAAM2-related disorder	Benign (Feb 19, 2019)
6-39856353-C-T		DAAM2-related disorder	Benign (Feb 24, 2020)
6-39856354-G-A		DAAM2-related disorder	Benign/Likely benign (Feb 19, 2019)
6-39856384-C-T		Inborn genetic diseases	Uncertain significance (May 04, 2022)
6-39856431-G-A		DAAM2-related disorder	Likely benign (Apr 07, 2022)
6-39856434-C-T		DAAM2-related disorder	Likely benign (Jul 07, 2023)
6-39860967-T-C		Inborn genetic diseases	Uncertain significance (Dec 01, 2022)
6-39860979-C-A		Nephrotic syndrome, type 24 • DAAM2-related disorder	Uncertain significance (Feb 26, 2024)
6-39864446-C-T			Uncertain significance (Dec 01, 2016)
6-39864487-C-T		Inborn genetic diseases	Uncertain significance (May 26, 2022)
6-39864488-G-A		DAAM2-related disorder	Benign (May 24, 2019)
6-39865007-G-C		Nephrotic syndrome, type 24	Pathogenic (Apr 08, 2021)
6-39865058-C-T		Inborn genetic diseases	Uncertain significance (Nov 03, 2022)
6-39865059-G-A		Inborn genetic diseases	Uncertain significance (Jul 26, 2021)
6-39867500-T-C			Benign (Dec 31, 2019)
6-39867587-G-C		Inborn genetic diseases	Uncertain significance (Aug 04, 2023)
6-39867595-C-T		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
6-39867596-G-A		DAAM2-related disorder	Benign (Jul 30, 2019)
6-39867673-C-T		Inborn genetic diseases	Uncertain significance (Jan 23, 2024)
6-39867706-C-G		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
6-39867814-G-C		DAAM2-related disorder	Benign (Feb 18, 2019)
6-39867821-C-T		Inborn genetic diseases	Uncertain significance (Sep 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DAAM2	protein_coding	protein_coding	ENST00000398904	24	112507

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.97e-8	124140	0	3	124143	0.0000121

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.27	535	624	0.857	0.0000391	6977
Missense in Polyphen		267	324.5	0.82281		3792
Synonymous	0.797	222	238	0.934	0.0000135	2031
Loss of Function	6.45	1	50.4	0.0198	0.00000241	610

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000649	0.0000648
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000178
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key regulator of the Wnt signaling pathway, which is required for various processes during development, such as dorsal patterning, determination of left/right symmetry or myelination in the central nervous system. Acts downstream of Wnt ligands and upstream of beta-catenin (CTNNB1). Required for canonical Wnt signaling pathway during patterning in the dorsal spinal cord by promoting the aggregation of Disheveled (Dvl) complexes, thereby clustering and formation of Wnt receptor signalosomes and potentiating Wnt activity. During dorsal patterning of the spinal cord, inhibits oligodendrocytes differentiation via interaction with PIP5K1A. Also regulates non-canonical Wnt signaling pathway. Acts downstream of PITX2 in the developing gut and is required for left/right asymmetry within dorsal mesentery: affects mesenchymal condensation by lengthening cadherin-based junctions through WNT5A and non-canonical Wnt signaling, inducing polarized condensation in the left dorsal mesentery necessary to initiate gut rotation. Together with DAAM1, required for myocardial maturation and sarcomere assembly. {ECO:0000250|UniProtKB:Q80U19}.
• Pathway: Wnt signaling pathway - Homo sapiens (human);Wnt Signaling Pathway (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.195
• rvis_EVS: 0.04
• rvis_percentile_EVS: 56.27

Haploinsufficiency Scores

• pHI: 0.206
• hipred: Y
• hipred_score: 0.644
• ghis: 0.464

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.214

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Daam2
• Phenotype: skeleton phenotype; 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); homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: determination of left/right symmetry;Wnt signaling pathway;dorsal spinal cord development;actin cytoskeleton organization;negative regulation of oligodendrocyte differentiation;regulation of canonical Wnt signaling pathway;positive regulation of canonical Wnt signaling pathway;regulation of non-canonical Wnt signaling pathway
• Cellular component: extracellular exosome
• Molecular function: actin binding;Rho GTPase binding