Submissions for variant NM_022489.4(INF2):c.2885A>C (p.Lys962Thr)

gnomAD frequency: 0.00023  dbSNP: rs376067427

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001810994	SCV000604028	uncertain significance	not provided	2020-03-06	criteria provided, single submitter	clinical testing	The INF2 c.2885A>C; p.Lys962Thr variant (rs376067427), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 439827). This variant is found in the non-Finnish European population with an overall allele frequency of 0.03% (36/124886 alleles) in the Genome Aggregation Database. The lysine at codon 962 is moderately conserved, but computational analyses (SIFT: tolerated, PolyPhen-2: damaging) predict conflicting effects of this variant on protein structure/function. However, given the lack of clinical and functional data, the significance of the p.Lys962Thr variant is uncertain at this time.
Invitae	RCV000649981	SCV000771818	likely benign	Focal segmental glomerulosclerosis 5; Charcot-Marie-Tooth disease dominant intermediate E	2023-12-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001113917	SCV001271730	benign	Focal segmental glomerulosclerosis 5	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.
Ambry Genetics	RCV002438233	SCV002750493	likely benign	Inborn genetic diseases	2020-02-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003419879	SCV004116548	uncertain significance	INF2-related condition	2022-12-19	criteria provided, single submitter	clinical testing	The INF2 c.2885A>C variant is predicted to result in the amino acid substitution p.Lys962Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.029% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-105179788-A-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.