Submissions for variant NM_018489.3(ASH1L):c.4902_4903del (p.Ser1635fs)

dbSNP: rs1665684529

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001236387	SCV001409110	pathogenic	not provided	2019-10-25	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ASH1L are known to be pathogenic (PMID: 29276005). This variant has not been reported in the literature in individuals with ASH1L-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser1635Cysfs*18) in the ASH1L gene. It is expected to result in an absent or disrupted protein product.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV001814286	SCV002061583	likely pathogenic	Intellectual disability, autosomal dominant 52	2021-09-10	criteria provided, single submitter	clinical testing	PVS1, PM2
Genome-Nilou Lab	RCV001814286	SCV004050412	likely pathogenic	Intellectual disability, autosomal dominant 52	2023-04-11	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004528429	SCV004111690	likely pathogenic	ASH1L-related disorder	2023-03-15	criteria provided, single submitter	clinical testing	The ASH1L c.4902_4903delTT variant is predicted to result in a frameshift and premature protein termination (p.Ser1635Cysfs*18). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic/likely pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/962517/). Frameshift variants in ASH1L are expected to be pathogenic. This variant is interpreted as likely pathogenic.
GenomeConnect - Brain Gene Registry	RCV001814286	SCV003927995	not provided	Intellectual disability, autosomal dominant 52		no assertion provided	phenotyping only	Variant interpreted as pathogenic and reported on 2019-11-01 by Invitae. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect.”)
GenomeConnect - Invitae Patient Insights Network	RCV001814286	SCV004228660	not provided	Intellectual disability, autosomal dominant 52		no assertion provided	phenotyping only	Variant interpreted as Pathogenic and reported on 11-01-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.