ADGRG2

adhesion G protein-coupled receptor G2, the group of Adhesion G protein-coupled receptors, subfamily G

Basic information

Region (hg38): X:18989307-19122637

Previous symbols: [ "GPR64" ]

Links

ENSG00000173698 ∙ NCBI:10149 ∙ OMIM:300572 ∙ HGNC:4516 ∙ Uniprot:Q8IZP9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital bilateral absence of vas deferens (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vas deferens, congenital bilateral aplasia of, X-linked	XL	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	Genitourinary	27476656

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ADGRG2 gene.

• Congenital bilateral aplasia of vas deferens from CFTR mutation (9 variants)
• Vas deferens, congenital bilateral aplasia of, X-linked (3 variants)
• Obstructive azoospermia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ADGRG2 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				6	1	7
missense			28	9	2	39
nonsense	2					2
start loss						0
frameshift	7					7
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding				1		1
Total	9	0	28	16	3

Variants in ADGRG2

This is a list of pathogenic ClinVar variants found in the ADGRG2 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-18990883-T-C		Inborn genetic diseases	Uncertain significance (Aug 08, 2022)
X-18990922-C-T		Inborn genetic diseases	Uncertain significance (May 15, 2024)
X-18994908-C-T		Inborn genetic diseases	Uncertain significance (Sep 22, 2022)
X-18994919-CA-C		Congenital bilateral aplasia of vas deferens from CFTR mutation • Vas deferens, congenital bilateral aplasia of, X-linked	Pathogenic (Apr 12, 2016)
X-18995036-G-A		Inborn genetic diseases	Uncertain significance (Mar 05, 2024)
X-18995052-C-A		ADGRG2-related disorder	Likely benign (Jul 11, 2019)
X-18996063-C-T		Inborn genetic diseases	Uncertain significance (Apr 13, 2022)
X-18996068-C-T			Likely benign (Feb 01, 2023)
X-18996069-G-A		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
X-18996092-C-T			Likely benign (Dec 31, 2019)
X-18999137-G-A		Congenital bilateral aplasia of vas deferens from CFTR mutation	Pathogenic (Sep 01, 2017)
X-18999154-T-G		Inborn genetic diseases	Uncertain significance (Dec 19, 2023)
X-18999250-T-C		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
X-18999251-A-G		Inborn genetic diseases	Uncertain significance (Dec 20, 2021)
X-18999879-T-C			Benign (Dec 31, 2019)
X-18999886-A-T		Inborn genetic diseases	Uncertain significance (Mar 07, 2023)
X-18999892-C-T		Inborn genetic diseases	Uncertain significance (May 09, 2024)
X-19002891-T-C		Vas deferens, congenital bilateral aplasia of, X-linked	Uncertain significance (Oct 09, 2023)
X-19002979-T-TA		Congenital bilateral aplasia of vas deferens from CFTR mutation	Pathogenic (Sep 01, 2017)
X-19003007-A-G		Inborn genetic diseases	Likely benign (Jan 23, 2023)
X-19003013-T-A		Inborn genetic diseases	Uncertain significance (Apr 16, 2024)
X-19003041-AGA-CAGAGCAATCCACGAGT		Obstructive azoospermia	Pathogenic (Aug 23, 2021)
X-19003048-G-A		ADGRG2-related disorder	Likely benign (Jul 01, 2019)
X-19003060-C-G			Likely benign (Mar 06, 2018)
X-19003068-C-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ADGRG2	protein_coding	protein_coding	ENST00000379869	27	133329

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.927	0.0731	125705	5	6	125716	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.89	267	369	0.724	0.0000273	6623
Missense in Polyphen		73	123.79	0.58973		2383
Synonymous	0.462	139	146	0.951	0.0000114	2054
Loss of Function	4.52	6	34.8	0.172	0.00000246	639

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000147	0.000147
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000396	0.0000264
Middle Eastern	0.000218	0.000163
South Asian	0.000118	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Orphan receptor. Could be involved in a signal transduction pathway controlling epididymal function and male fertility. May regulate fluid exchange within epididymis. {ECO:0000250|UniProtKB:Q8CJ12}.
• Disease: DISEASE: Congenital bilateral aplasia of the vas deferens, X- linked (CBAVDX) [MIM:300985]: A disease characterized by bilateral absence of vas deferens, obstructive azoospermia, and infertility. {ECO:0000269|PubMed:27476656}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: GPCRs, Class B Secretin-like (Consensus)

Recessive Scores

• pRec: 0.104

Intolerance Scores

• rvis_EVS: 0.51
• rvis_percentile_EVS: 80.24

Haploinsufficiency Scores

• pHI: 0.540
• hipred: Y
• hipred_score: 0.579
• ghis: 0.400

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Adgrg2
• Phenotype: reproductive system phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: cell surface receptor signaling pathway;G protein-coupled receptor signaling pathway;adenylate cyclase-activating G protein-coupled receptor signaling pathway;spermatogenesis
• Cellular component: cytosol;plasma membrane;integral component of plasma membrane;cell surface;integral component of membrane;apical plasma membrane;extracellular exosome
• Molecular function: G protein-coupled receptor activity