Submissions for variant NM_030632.3(ASXL3):c.4219_4220del (p.Leu1407fs)

dbSNP: rs1555744178

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000627525	SCV000748525	pathogenic	not provided	2024-09-05	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation, as the last 842 amino acids are replaced with 19 different amino acids, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33057194, 35982159, 24077912, 28333917, 34436830)
CeGaT Center for Human Genetics Tuebingen	RCV000627525	SCV001335077	pathogenic	not provided	2020-02-01	criteria provided, single submitter	clinical testing
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV001265438	SCV005420551	pathogenic	Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome	2024-10-04	criteria provided, single submitter	research	PVS1,PS2,PM2
GenomeConnect - Simons Searchlight	RCV001265438	SCV001443569	pathogenic	Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome	2019-03-04	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2019-03-04 and interpreted as Pathogenic. Variant was initially reported on 2019-01-25 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.
Solve-RD Consortium	RCV001265438	SCV005200053	likely pathogenic	Severe feeding difficulties-failure to thrive-microcephaly due to ASXL3 deficiency syndrome	2022-06-01	no assertion criteria provided	provider interpretation	Variant confirmed as disease-causing by referring clinical team
PreventionGenetics, part of Exact Sciences	RCV004748866	SCV005361057	pathogenic	ASXL3-related disorder	2024-09-18	no assertion criteria provided	clinical testing	The ASXL3 c.4219_4220delCT variant is predicted to result in a frameshift and premature protein termination (p.Leu1407Glyfs*20). This variant has been reported in the de novo state in multiple individuals with ASXL3-related syndrome (Schirwani et al 2021. PubMed ID: 34436830; Vissers et al. 2017. PubMed ID: 28333917). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in ASXL3 are expected to be pathogenic. This variant is interpreted as pathogenic.