SHLD2

shieldin complex subunit 2, the group of Shieldin complex

Basic information

Region (hg38): 10:87094161-87191465

Previous symbols: [ "FAM35A" ]

Links

ENSG00000122376 ∙ NCBI:54537 ∙ OMIM:618029 ∙ HGNC:28773 ∙ Uniprot:Q86V20 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SHLD2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHLD2 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						0
missense			42	2	1	45
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	42	2	1

Variants in SHLD2

This is a list of pathogenic ClinVar variants found in the SHLD2 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-87094318-C-T		not specified	Uncertain significance (Jun 24, 2015)
10-87094320-C-CTCA		GLUD1-related disorder	Uncertain significance (Dec 07, 2022)
10-87094338-C-A		Hyperinsulinism-hyperammonemia syndrome	Likely benign (Nov 25, 2020)
10-87094355-G-A		Hyperinsulinism-hyperammonemia syndrome	Uncertain significance (Apr 06, 2021)
10-87094364-G-T		Hyperinsulinism-hyperammonemia syndrome	Likely benign (Mar 01, 2019)
10-87094377-G-C		not specified • Hyperinsulinism-hyperammonemia syndrome • Inborn genetic diseases	Conflicting classifications of pathogenicity (May 30, 2024)
10-87094394-C-T		not specified • Monogenic diabetes • Hyperinsulinism-hyperammonemia syndrome	Benign/Likely benign (Jan 13, 2024)
10-87094414-G-C			Likely benign (-)
10-87094428-A-G		not specified • Hyperinsulinism-hyperammonemia syndrome	Benign (Jan 08, 2024)
10-87094440-C-T		Hyperinsulinism-hyperammonemia syndrome	Conflicting classifications of pathogenicity (Aug 27, 2022)
10-87094445-T-A		Inborn genetic diseases	Uncertain significance (Jun 16, 2023)
10-87094463-G-C		Hyperinsulinism-hyperammonemia syndrome	Uncertain significance (Jun 23, 2022)
10-87094468-C-G		not specified	Uncertain significance (Apr 10, 2024)
10-87094473-C-G		Hyperinsulinism-hyperammonemia syndrome	Likely benign (Jun 22, 2022)
10-87094485-C-T			Likely benign (Sep 19, 2018)
10-87094496-G-A		Inborn genetic diseases	Uncertain significance (Sep 19, 2022)
10-87094497-G-A		Hyperinsulinism-hyperammonemia syndrome	Likely benign (Jan 19, 2023)
10-87094499-T-A			Uncertain significance (Mar 14, 2023)
10-87094523-C-T		Hyperinsulinism-hyperammonemia syndrome	Uncertain significance (Oct 21, 2022)
10-87094530-G-C		Hyperinsulinism-hyperammonemia syndrome	Uncertain significance (Apr 09, 2021)
10-87094542-G-A			Likely benign (Jun 26, 2018)
10-87094544-G-A		Hyperinsulinism-hyperammonemia syndrome	Uncertain significance (Mar 31, 2020)
10-87094554-G-C		Inborn genetic diseases	Likely benign (Dec 05, 2019)
10-87094558-T-G		Hyperinsulinism-hyperammonemia syndrome	Uncertain significance (Jul 29, 2023)
10-87094560-C-T		Inborn genetic diseases	Likely benign (Jul 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SHLD2	protein_coding	protein_coding	ENST00000298784	7	97308

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000124	0.990	125569	0	17	125586	0.0000677

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.382	350	371	0.944	0.0000177	5485
Missense in Polyphen		85	92.907	0.91489		1489
Synonymous	-0.827	148	136	1.09	0.00000693	1568
Loss of Function	2.31	12	24.3	0.494	0.00000102	394

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000103	0.0000924
European (Non-Finnish)	0.0000815	0.0000793
Middle Eastern	0.00	0.00
South Asian	0.0000361	0.0000327
Other	0.000170	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs) (PubMed:29656893, PubMed:29789392). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection (PubMed:29656893, PubMed:29789392). Mediates various NHEJ- dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres (PubMed:29656893). {ECO:0000269|PubMed:29656893, ECO:0000269|PubMed:29789392}.

Recessive Scores

• pRec: 0.0793

Intolerance Scores

• rvis_EVS: -0.07
• rvis_percentile_EVS: 48.69

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.357
• ghis: 0.571

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Shld2

Gene ontology

• Biological process: DNA repair;positive regulation of isotype switching;negative regulation of double-strand break repair via homologous recombination;positive regulation of double-strand break repair via nonhomologous end joining
• Cellular component: nucleus;chromosome;site of double-strand break
• Molecular function: protein binding