Submissions for variant NM_004984.4(KIF5A):c.152G>A (p.Arg51His)

gnomAD frequency: 0.00010  dbSNP: rs773336059

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001111425	SCV001268982	likely benign	Hereditary spastic paraplegia 10	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002069798	SCV002453525	benign	Spastic paraplegia	2025-01-22	criteria provided, single submitter	clinical testing
GeneDx	RCV002298873	SCV002588002	uncertain significance	not provided	2022-04-25	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV003246695	SCV003950781	uncertain significance	Inborn genetic diseases	2023-04-20	criteria provided, single submitter	clinical testing	The c.152G>A (p.R51H) alteration is located in exon 2 (coding exon 2) of the KIF5A gene. This alteration results from a G to A substitution at nucleotide position 152, causing the arginine (R) at amino acid position 51 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004547987	SCV004735438	likely benign	KIF5A-related disorder	2023-06-22	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).