Submissions for variant NM_018136.5(ASPM):c.2267A>G (p.Tyr756Cys)

gnomAD frequency: 0.00031  dbSNP: rs201066146

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000400932	SCV000352731	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.
Invitae	RCV000920873	SCV001066258	benign	not provided	2023-12-07	criteria provided, single submitter	clinical testing
GeneDx	RCV000920873	SCV001890256	likely benign	not provided	2019-02-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002519465	SCV003750181	likely benign	Inborn genetic diseases	2022-02-10	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.
CeGaT Center for Human Genetics Tuebingen	RCV000920873	SCV004125203	likely benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	ASPM: BS2
Genome-Nilou Lab	RCV000400932	SCV004178730	likely benign	Microcephaly 5, primary, autosomal recessive	2023-04-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003930218	SCV004742608	benign	ASPM-related condition	2020-01-28	criteria provided, single submitter	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).