Submissions for variant NM_018136.5(ASPM):c.8452G>T (p.Ala2818Ser)

gnomAD frequency: 0.00021  dbSNP: rs188955444

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000597987	SCV000704907	uncertain significance	not provided	2017-01-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000597987	SCV001039507	likely benign	not provided	2023-11-12	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470922	SCV002768648	uncertain significance	Microcephaly 5, primary, autosomal recessive	2019-08-28	criteria provided, single submitter	clinical testing	A heterozygous missense variant, NM_018136.4(ASPM):c.8452G>T, has been identified in exon 18 of 28 of the ASPM gene. The variant is predicted to result in a moderate amino acid change from alanine to serine at position 2818 of the protein (NP_060606.3(ASPM):p.(Ala2818Ser)). The alanine residue at this position has low conservation (100 vertebrates, UCSC), but is not located within a well established functional domain. In silico predictions of pathogenicity for this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD database at a frequency of 0.05% (153 heterozygotes, 0 homozygotes) and has been previously described as a variant of uncertain significance (ClinVar). Based on the information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS).
PreventionGenetics, part of Exact Sciences	RCV003952968	SCV004784358	benign	ASPM-related disorder	2019-02-28	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).