Submissions for variant NM_001558.4(IL10RA):c.781C>T (p.Arg261Trp)

gnomAD frequency: 0.00023  dbSNP: rs201396764

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000238699	SCV000297101	uncertain significance	not specified	2015-10-04	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001087846	SCV000367434	uncertain significance	Inflammatory bowel disease 28	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000767103	SCV000621133	uncertain significance	not provided	2017-09-27	criteria provided, single submitter	clinical testing	The R261W variant in the IL10RA gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is observed in 43/10,152 alleles (0.4%) from individuals of Ashkenazi Jewish background, and 117/276,954 global alleles (0.04%), in large population cohorts (Lek et al., 2016). The R261W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The R261W variant is reported as a variant of uncertain significance in ClinVar by different clinical laboratories, but additional evidence is not available (ClinVar SCV000297101.2, SCV000367434.2; Landrum et al., 2016). We also interpret R261W as a variant of uncertain significance.
Invitae	RCV001087846	SCV000814870	likely benign	Inflammatory bowel disease 28	2024-01-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000767103	SCV004136151	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	IL10RA: BP4