Submissions for variant NM_018136.5(ASPM):c.3599-4A>G

gnomAD frequency: 0.00284  dbSNP: rs149303254

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145114	SCV000192157	uncertain significance	Microcephaly 5, primary, autosomal recessive	2013-02-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000214044	SCV000278794	uncertain significance	not specified	2017-09-26	criteria provided, single submitter	clinical testing	The c.3599-4 A>G variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI Exome Sequencing Project reports c.3599-4 A>G was observed in 40/4404 (0.9%) alleles from individuals of African American background. Additionally, the 1000 Genomes Project reports it was observed in 3/448 (0.7%) alleles from individuals of African background and in 1/196 (0.5%) alleles from individuals of Italian background, indicating it may be a rare (benign) variant in these populations. Several in-silico splice prediction models predict that c.3599-4 A>G creates a cryptic acceptor site which may supplant or damage the natural acceptor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Eurofins Ntd Llc (ga)	RCV000214044	SCV000339189	likely benign	not specified	2016-01-29	criteria provided, single submitter	clinical testing
Invitae	RCV000961914	SCV001108970	benign	not provided	2023-12-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000961914	SCV004125201	likely benign	not provided	2022-06-01	criteria provided, single submitter	clinical testing	ASPM: PP3, BS2
PreventionGenetics, part of Exact Sciences	RCV003945162	SCV004766373	likely benign	ASPM-related condition	2019-03-15	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).