Submissions for variant NM_001370466.1(NOD2):c.2087C>T (p.Pro696Leu)

gnomAD frequency: 0.00011  dbSNP: rs201076024

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002537205	SCV000945510	likely benign	Blau syndrome; Regional enteritis	2023-10-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001115355	SCV001273326	benign	Blau syndrome	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001784427	SCV001273327	uncertain significance	Inflammatory bowel disease 1	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.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002261221	SCV002542680	uncertain significance	Autoinflammatory syndrome	2020-03-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002534810	SCV003707583	uncertain significance	Inborn genetic diseases	2021-08-23	criteria provided, single submitter	clinical testing	The c.2168C>T (p.P723L) alteration is located in exon 4 (coding exon 4) of the NOD2 gene. This alteration results from a C to T substitution at nucleotide position 2168, causing the proline (P) at amino acid position 723 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529368	SCV001742694	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529368	SCV001974359	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003892723	SCV004717588	uncertain significance	NOD2-related disorder	2024-01-16	no assertion criteria provided	clinical testing	The NOD2 c.2168C>T variant is predicted to result in the amino acid substitution p.Pro723Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.055% of alleles in individuals of East Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.