Submissions for variant NM_001243133.2(NLRP3):c.2176A>G (p.Ser726Gly)

gnomAD frequency: 0.00049  dbSNP: rs147946775

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001172030	SCV000278947	likely benign	not provided	2021-04-21	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25821352)
Illumina Laboratory Services, Illumina	RCV000303538	SCV000356983	likely benign	Familial amyloid nephropathy with urticaria AND deafness	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000626053	SCV000356984	likely benign	Familial cold autoinflammatory syndrome 1	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000263610	SCV000356985	likely benign	Chronic infantile neurological, cutaneous and articular syndrome	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001172030	SCV000604552	likely benign	not provided	2023-04-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000552226	SCV000646267	likely benign	Cryopyrin associated periodic syndrome	2024-01-19	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV000626053	SCV000746675	uncertain significance	Familial cold autoinflammatory syndrome 1	2016-05-20	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000216458	SCV000967262	likely benign	not specified	2018-04-12	criteria provided, single submitter	clinical testing	The p.Ser728Gly variant is classified as likely benign because it has been ident ified in 0.08% (105/126674) of European chromosomes by the Genome Aggregation Da tabase (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs147946775). It has bee n reported in one individual with PFAPA, but was also identified in 2 unaffected family members (Perko 2015). ACMG/AMP Criteria applied: BS1.
CeGaT Center for Human Genetics Tuebingen	RCV001172030	SCV001334959	benign	not provided	2023-07-01	criteria provided, single submitter	clinical testing	NLRP3: BP4, BS1, BS2
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002262814	SCV002542616	likely benign	Autoinflammatory syndrome	2020-01-01	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000216458	SCV004243538	uncertain significance	not specified	2024-02-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004532811	SCV004733406	likely benign	NLRP3-related disorder	2022-09-23	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001172030	SCV001978086	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001172030	SCV001980001	likely benign	not provided		no assertion criteria provided	clinical testing