SMARCD2

SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2, the group of BAF complex|GBAF complex|PBAF complex

Basic information

Region (hg38): 17:63832080-63843065

Links

ENSG00000108604 ∙ NCBI:6603 ∙ OMIM:601736 ∙ HGNC:11107 ∙ Uniprot:Q92925 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• specific granule deficiency (Supportive), mode of inheritance: AR
• specific granule deficiency 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Specific granule defiency 2	AR	Allergy/Immunology/Infectious	Among other findings, individuals have been described with early-onset severe and recurrent infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; HSCT has been described	Allergy/Immunology/Infectious; Craniofacial; Hematologic; Musculoskeletal; Neurologic	28369036

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMARCD2 gene.

• not provided (221 variants)
• Inborn genetic diseases (16 variants)
• Specific granule deficiency 2 (6 variants)
• SMARCD2-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMARCD2 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				52	4	56
missense			88		4	92
nonsense	5	2				7
start loss						0
frameshift	5	1	1			7
inframe indel			4			4
splice donor/acceptor (+/-2bp)	1	3				4
splice region			7	12		19
non coding	1	1	1	40	2	45
Total	12	7	94	92	10

Highest pathogenic variant AF is 0.00000657

Variants in SMARCD2

This is a list of pathogenic ClinVar variants found in the SMARCD2 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-63832948-C-G			Uncertain significance (Aug 21, 2022)
17-63832948-C-T			Uncertain significance (Dec 07, 2023)
17-63832953-T-A			Likely benign (Oct 09, 2022)
17-63832989-C-T		Specific granule deficiency 2 • SMARCD2-related disorder	Benign/Likely benign (Jan 30, 2024)
17-63832999-A-C		SMARCD2-related disorder	Likely benign (Dec 02, 2023)
17-63833002-G-A			Likely benign (Jul 25, 2023)
17-63833006-A-C			Likely benign (Oct 23, 2023)
17-63833049-A-G			Likely benign (Jan 16, 2022)
17-63833062-G-A			Likely benign (Jan 16, 2023)
17-63833062-G-C			Likely benign (Sep 12, 2023)
17-63833069-C-A			Uncertain significance (Sep 24, 2021)
17-63833075-A-G			Likely benign (Dec 09, 2023)
17-63833079-A-G		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)
17-63833130-C-T			Uncertain significance (Mar 10, 2022)
17-63833131-G-A			Pathogenic (Oct 19, 2020)
17-63833134-TCTC-T			Uncertain significance (May 18, 2021)
17-63833136-TCC-T			Uncertain significance (Apr 12, 2022)
17-63833140-C-T			Uncertain significance (Feb 03, 2023)
17-63833144-A-C			Likely benign (Apr 12, 2022)
17-63833147-A-G			Likely benign (Jan 20, 2021)
17-63833149-T-C			Uncertain significance (Jul 26, 2021)
17-63833154-A-G			Benign (Jan 29, 2024)
17-63833179-A-C			Likely benign (Jun 21, 2023)
17-63833187-G-A			Likely benign (Oct 03, 2023)
17-63833187-G-C			Likely benign (Jul 03, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMARCD2	protein_coding	protein_coding	ENST00000448276	13	10982

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000649	1.00	124677	0	18	124695	0.0000722

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.22	184	291	0.633	0.0000178	3421
Missense in Polyphen		81	141.15	0.57387		1606
Synonymous	0.714	99	108	0.913	0.00000655	1089
Loss of Function	3.24	13	33.1	0.393	0.00000235	298

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000126	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000556	0.0000556
Finnish	0.0000476	0.0000464
European (Non-Finnish)	0.0000893	0.0000884
Middle Eastern	0.0000556	0.0000556
South Asian	0.0000996	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:22952240, PubMed:26601204). Critical regulator of myeloid differentiation, controlling granulocytopoiesis and the expression of genes involved in neutrophil granule formation (PubMed:28369036). {ECO:0000269|PubMed:28369036, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.
• Disease: DISEASE: Specific granule deficiency 2 (SGD2) [MIM:617475]: A form of specific granule deficiency, an autosomal recessive disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. SGD2 is due to defective neutrophil development. Bone marrow findings include hypercellularity, abnormal megakaryocytes, and features of progressive myelofibrosis with blasts. Some patients may have additional findings, including delayed development, mild dysmorphic features, and distal skeletal anomalies. {ECO:0000269|PubMed:28369036}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thermogenesis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Androgen Receptor Network in Prostate Cancer;Tumor suppressor activity of SMARCB1;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Generic Transcription Pathway;RNA Polymerase II Transcription;RMTs methylate histone arginines;Chromatin modifying enzymes;Chromatin organization;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.58

Haploinsufficiency Scores

• pHI: 0.952
• hipred: Y
• hipred_score: 0.775
• ghis: 0.511

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Smarcd2
• Phenotype: vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: smarcd2
• Affected structure: neutrophil
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: nucleosome disassembly;chromatin remodeling;regulation of transcription by RNA polymerase II;ATP-dependent chromatin remodeling;positive regulation of nucleic acid-templated transcription
• Cellular component: nuclear chromatin;nucleoplasm;SWI/SNF complex;protein-containing complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;transcription coactivator activity;protein binding;nucleosomal DNA binding