Submissions for variant NM_181078.3(IL21R):c.824G>A (p.Arg275Gln)

gnomAD frequency: 0.00673  dbSNP: rs52822694

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000239104	SCV000297397	uncertain significance	not specified	2015-11-24	criteria provided, single submitter	clinical testing
Invitae	RCV001082158	SCV000653614	benign	Cryptosporidiosis-chronic cholangitis-liver disease syndrome	2024-01-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000531186	SCV001150876	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	IL21R: BP4, BS1, BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000531186	SCV001157298	likely benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002518530	SCV003542325	likely benign	Inborn genetic diseases	2021-08-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224239	SCV003920064	uncertain significance	IgE responsiveness, atopic; Cryptosporidiosis-chronic cholangitis-liver disease syndrome	2021-03-30	criteria provided, single submitter	clinical testing	IL21R NM_021798.3 exon 8 p.Arg275Gln (c.824G>A): This variant has not been reported in the literature but is present in 0.9% (1254/128760) of European alleles, including 9 homozygotes in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/16-27457366-G-A). This variant is present in ClinVar (Variation ID: 252799). This variant amino acid Glutamine (Gln) is present in >10 species and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.