ClinVar Miner

Submissions for variant NM_022162.3(NOD2):c.2546C>T (p.Ala849Val) (rs104895486)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000381377 SCV000397283 likely benign Blau syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000285499 SCV000397284 likely benign Crohn disease 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000808553 SCV000948663 uncertain significance Blau syndrome; Inflammatory bowel disease 1 2018-12-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 849 of the NOD2 protein (p.Ala849Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs104895486, ExAC 0.05%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in an individual with Crohn's disease, however this individual also carried the common p.Leu1007Profs*2 variant, which is known to be associated with Crohn's disease (PMID: 16485124). ClinVar contains an entry for this variant (Variation ID: 97855). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084112 SCV000116243 not provided Sarcoidosis, early-onset no assertion provided not provided

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