Submissions for variant NM_018136.5(ASPM):c.7114A>G (p.Arg2372Gly)

gnomAD frequency: 0.00031  dbSNP: rs190693455

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000593394	SCV000704911	uncertain significance	not provided	2017-01-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000593394	SCV001039508	likely benign	not provided	2024-11-13	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470923	SCV002766715	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.7114A>G, has been identified in exon 18 of 28 of the ASPM gene. The variant is predicted to result in a major amino acid change from arginine to glycine at position 2372 of the protein (NP_060606.3(ASPM):p.Arg2372Gly). The arginine residue at this position has low conservation (100 vertebrates, UCSC), and is located within the COG5022 super family 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	RCV003962687	SCV004782880	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).