Submissions for variant NM_001370466.1(NOD2):c.2631G>A (p.Leu877=)

gnomAD frequency: 0.00012  dbSNP: rs142559533

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000272343	SCV000397295	benign	Blau syndrome	2018-01-13	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	RCV001782834	SCV000397296	uncertain significance	Inflammatory bowel disease 1	2018-01-13	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002521046	SCV001534017	likely benign	Blau syndrome; Regional enteritis	2024-05-01	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV002056496	SCV002495874	uncertain significance	Blau syndrome; Psoriatic arthritis, susceptibility to; Yao syndrome; Inflammatory bowel disease 1		criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in 0.006% (1/15280) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-50720006-G-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:319472). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224259	SCV003920297	uncertain significance	Blau syndrome; Yao syndrome; Inflammatory bowel disease 1		criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in 0.006% (1/15280) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-50720006-G-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:319472). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CeGaT Center for Human Genetics Tuebingen	RCV005256597	SCV005910124	likely benign	not provided	2025-03-01	criteria provided, single submitter	clinical testing	NOD2: BP4, BP7, BS1