NHLRC2

NHL repeat containing 2

Basic information

Region (hg38): 10:113854660-113917194

Links

ENSG00000196865 ∙ NCBI:374354 ∙ OMIM:618277 ∙ HGNC:24731 ∙ Uniprot:Q8NBF2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• fibrosis, neurodegeneration, and cerebral angiomatosis (Limited), mode of inheritance: AR
• fibrosis, neurodegeneration, and cerebral angiomatosis (Definitive), mode of inheritance: AR
• fibrosis, neurodegeneration, and cerebral angiomatosis (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fibrosis, neurodegeneration, and cerebral angiomatosis	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	Allergy/Immunology/Infectious; Cardiovascular; Gastrointestinal; Hematologic; Neurologic; Pulmonary	29423877

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NHLRC2 gene.

• Inborn genetic diseases (24 variants)
• Fibrosis, neurodegeneration, and cerebral angiomatosis (9 variants)
• not provided (7 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NHLRC2 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				2		2
missense	1		24	2		27
nonsense	1					1
start loss						0
frameshift		2				2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	2	2	25	4	0

Highest pathogenic variant AF is 0.000433

Variants in NHLRC2

This is a list of pathogenic ClinVar variants found in the NHLRC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-113854873-A-G		Fibrosis, neurodegeneration, and cerebral angiomatosis	Conflicting classifications of pathogenicity (Apr 25, 2022)
10-113854931-C-T		Inborn genetic diseases	Uncertain significance (Feb 27, 2024)
10-113854966-CAGG-C		Fibrosis, neurodegeneration, and cerebral angiomatosis	Uncertain significance (-)
10-113854988-A-G		Inborn genetic diseases	Uncertain significance (Feb 01, 2023)
10-113854991-A-G		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
10-113855020-C-T		Fibrosis, neurodegeneration, and cerebral angiomatosis	Pathogenic (Nov 03, 2021)
10-113855031-A-T			Likely benign (Feb 01, 2024)
10-113858566-T-A		Inborn genetic diseases	Uncertain significance (Oct 12, 2022)
10-113858573-A-T		Fibrosis, neurodegeneration, and cerebral angiomatosis	Pathogenic (Sep 20, 2021)
10-113858593-G-C		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
10-113858625-CTG-C		See cases	Likely pathogenic (Jun 03, 2020)
10-113876533-T-C		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
10-113876567-A-G			Likely benign (Jun 01, 2022)
10-113876617-A-C		Fibrosis, neurodegeneration, and cerebral angiomatosis	Pathogenic (Sep 20, 2021)
10-113876622-A-G		Inborn genetic diseases	Likely benign (Jun 17, 2022)
10-113876631-G-T		Fibrosis, neurodegeneration, and cerebral angiomatosis	Pathogenic (May 16, 2023)
10-113876643-A-G		Inborn genetic diseases	Uncertain significance (Jan 27, 2022)
10-113876696-A-T		NHLRC2-related disorder	Likely benign (Dec 09, 2019)
10-113876734-G-A		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
10-113876766-A-G		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
10-113876789-CAG-C		Fibrosis, neurodegeneration, and cerebral angiomatosis	Pathogenic (Jan 14, 2019)
10-113876796-C-A		Inborn genetic diseases	Uncertain significance (Apr 08, 2022)
10-113879589-G-C		Inborn genetic diseases	Uncertain significance (Feb 27, 2023)
10-113879639-G-A		NHLRC2-related disorder	Benign (Jun 13, 2019)
10-113879701-T-A		NHLRC2-related disorder	Benign (May 16, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NHLRC2	protein_coding	protein_coding	ENST00000369301	11	62534

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000832	0.999	125703	0	42	125745	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.742	328	368	0.891	0.0000169	4705
Missense in Polyphen		70	112.77	0.62074		1468
Synonymous	0.0897	137	138	0.990	0.00000674	1420
Loss of Function	2.95	14	32.0	0.437	0.00000148	425

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000204	0.000204
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000257	0.000255
Middle Eastern	0.000109	0.000109
South Asian	0.0000991	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Pathway: Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.0994

Intolerance Scores

• loftool: 0.467
• rvis_EVS: 0.67
• rvis_percentile_EVS: 84.61

Haploinsufficiency Scores

• pHI: 0.0847
• hipred: N
• hipred_score: 0.426
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.294

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nhlrc2
• 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)

Zebrafish Information Network

• Gene name: nhlrc2
• Affected structure: midbrain
• Phenotype tag: abnormal
• Phenotype quality: vacuolated

Gene ontology

• Biological process: platelet degranulation;cell redox homeostasis
• Cellular component: extracellular region;platelet alpha granule lumen
• Molecular function: protein binding