Submissions for variant NM_144687.4(NLRP12):c.910C>T (p.His304Tyr)

gnomAD frequency: 0.00392  dbSNP: rs141245482

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000249573	SCV000316036	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000525814	SCV000414554	benign	Familial cold autoinflammatory syndrome 2	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.
Invitae	RCV000525814	SCV000646339	benign	Familial cold autoinflammatory syndrome 2	2024-01-31	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000525814	SCV000782479	uncertain significance	Familial cold autoinflammatory syndrome 2	2016-08-02	criteria provided, single submitter	clinical testing
Mendelics	RCV000525814	SCV001142151	benign	Familial cold autoinflammatory syndrome 2	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000525814	SCV001160583	likely benign	Familial cold autoinflammatory syndrome 2	2023-10-09	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262907	SCV002542574	benign	Autoinflammatory syndrome	2022-05-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001706385	SCV002543975	benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	NLRP12: BP4, BS1, BS2
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000525814	SCV003920284	likely benign	Familial cold autoinflammatory syndrome 2	2022-10-13	criteria provided, single submitter	clinical testing	This variant has been reported in the literature in several individuals with features of immunodeficiency or autoimmunity, including periodic fevers, in the heterozygous and compound heterozygous state (Borte 2014 PMID: 25064829, Rusmini 2016 PMID: 26386126, Cetinkaya 2018 PMID: 29307770, Kostik 2018 PMID: 29500522, Ledesma 2019 PMID: 31836009, Suspitsin 2020 PMID: 32441320). This variant is present in the Genome Aggregation Database (Highest reported MAF: 2.1% [515/25100], including 3 homozygotes; https://gnomad.broadinstitute.org/variant/19-54314003-G-A?dataset=gnomad_r2_1). This variant is present in ClinVar, with several labs classifying this variant as likely benign or benign (Variation ID: 262532). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant suggests that this variant does not cause Mendelian disease but requires further evidence. Therefore, this variant is classified as likely benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001706385	SCV001926731	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001706385	SCV001971397	likely benign	not provided		no assertion criteria provided	clinical testing