Submissions for variant NM_018136.5(ASPM):c.7125_7128dup (p.Gln2377fs)

dbSNP: rs587783263

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145177	SCV000192226	pathogenic	Microcephaly 5, primary, autosomal recessive	2013-12-05	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000790789	SCV000345866	pathogenic	not provided	2016-09-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000790789	SCV001502569	pathogenic	not provided	2020-12-01	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000145177	SCV002019899	pathogenic	Microcephaly 5, primary, autosomal recessive	2021-01-29	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000145177	SCV002787127	likely pathogenic	Microcephaly 5, primary, autosomal recessive	2021-10-12	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000145177	SCV004178589	likely pathogenic	Microcephaly 5, primary, autosomal recessive	2023-04-11	criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV000145177	SCV004239052	pathogenic	Microcephaly 5, primary, autosomal recessive	2023-11-15	criteria provided, single submitter	clinical testing	This ASPM variant (rs587783263 ) is rare (<0.1%) in a large population dataset (gnomAD v4.0.0: 4/1461022 total alleles; 0.0003%; no homozygotes). It has been reported in ClinVar (Variation ID 157864), but has not been reported in the literature in individuals known to be affected with microcephaly and having biallelic ASPM variants, to our knowledge. This frameshift variant results in a premature stop codon in exon 18 of 28, likely leading to nonsense-mediated decay and lack of protein production. We consider c.7125_7128dup in ASPM to be pathogenic.