Submissions for variant NM_144687.4(NLRP12):c.3088C>G (p.Arg1030Gly)

dbSNP: rs201619538

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000967625	SCV000414511	benign	Familial cold autoinflammatory syndrome 2	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000967625	SCV001115016	benign	Familial cold autoinflammatory syndrome 2	2025-01-13	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000967625	SCV001472307	uncertain significance	Familial cold autoinflammatory syndrome 2	2019-10-21	criteria provided, single submitter	clinical testing	The NLRP12 c.3088C>G; p.Arg1030Gly variant (rs201619538) to our knowledge, is not reported in the medical literature or gene specific databases. The variant is reported in the ClinVar database (Variation ID: 330000) and in the South Asian population with an allele frequency of 0.6% (176/30604 alleles) in the Genome Aggregation Database. The arginine at codon 1030 is weakly conserved and computational analyses (SIFT: Damaging, PolyPhen-2: Benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Arg1030Gly variant is uncertain at this time.
GeneDx	RCV001764298	SCV001990871	uncertain significance	not provided	2019-04-02	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263049	SCV002542541	likely benign	Autoinflammatory syndrome	2021-04-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001764298	SCV002822597	benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	NLRP12: BP4, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003912380	SCV004730752	likely benign	NLRP12-related disorder	2024-01-20	no assertion criteria provided	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).