Submissions for variant NM_002661.5(PLCG2):c.77C>T (p.Thr26Met)

gnomAD frequency: 0.00058  dbSNP: rs189301790

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757665	SCV000885974	uncertain significance	not provided	2017-07-31	criteria provided, single submitter	clinical testing	The p.Thr26Met variant (rs189301790) has not been reported in the scientific medical literature or gene specific variant databases. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.06 percent (identified on 170 out of 277,184 chromosomes). Threonine at codon 26 is moderately conserved considering 11 species and Chinese hamster has methionine at this position suggesting that this amino acid change may be evolutionary tolerated. Additionally, computational analyses do not agree in their assessment of the impact of the variant on the protein (PolyPhen2: benign, SIFT: damaging, and Mutation Taster: disease causing). Altogether, the clinical significance of p.Thr26Met cannot be determined with certainty.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768282	SCV000898883	uncertain significance	Familial cold autoinflammatory syndrome 3; Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation	2021-03-30	criteria provided, single submitter	clinical testing	PLCG2 NM_002661.4 exon 2 p.Thr26Met (c.77C>T): This variant has not been reported in the literature but is present in 126/126700 European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs189301790). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086276	SCV001115088	likely benign	Familial cold autoinflammatory syndrome 3	2024-01-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000757665	SCV001247975	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	PLCG2: BS1, BS2