Submissions for variant NM_018136.5(ASPM):c.7475G>A (p.Arg2492Lys)

gnomAD frequency: 0.00037  dbSNP: rs118010078

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000175351	SCV000226824	benign	not specified	2015-05-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000175351	SCV000278800	uncertain significance	not specified	2014-10-10	criteria provided, single submitter	clinical testing	The R2492K variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, but the 1000 Genomes Project reports R2492K was observed in 2/178 (1.1%) alleles from individuals of Japanese background and in 1/194 (0.5%) alleles from individuals of Han Chinese background. The R2492K variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species; however Lysine has been observed at this position in one species in distant evolution. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Illumina Laboratory Services, Illumina	RCV000386579	SCV000352662	likely benign	Microcephaly 5, primary, autosomal recessive	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	RCV000906357	SCV001050988	benign	not provided	2024-12-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003947484	SCV004762156	benign	ASPM-related disorder	2019-10-03	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).