Submissions for variant NM_001172509.2(SATB2):c.715C>T (p.Arg239Ter)

dbSNP: rs137853127

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000256175	SCV000322291	pathogenic	not provided	2022-02-17	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate an abnormal truncated protein that forms a dimer with wild-type SATB2 and interferes with the activity of the wild-type protein suggesting a dominant-negative mechanism (Leoyklang et al., 2007; Leoyklang et al., 2013); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24363063, 31209962, 31144778, 23925499, 17377962, 25525159, 27774744, 28787087, 24301056, 30848049, 31021519)
Invitae	RCV000002627	SCV000835522	pathogenic	Chromosome 2q32-q33 deletion syndrome	2022-05-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg239*) in the SATB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SATB2 are known to be pathogenic (PMID: 25885067). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with a clinical phenotype including cleft palate, intellectual disability and epilepsy (PMID: 17377962, 24301056). ClinVar contains an entry for this variant (Variation ID: 2519). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000002627	SCV001429212	pathogenic	Chromosome 2q32-q33 deletion syndrome	2022-02-03	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PVS1, PS2, PS4_MOD, PS3_SUP, PM2_SUP
Diagnostic Laboratory, Strasbourg University Hospital	RCV001257620	SCV001434430	pathogenic	Intellectual disability	2020-04-20	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000256175	SCV001447251	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000002627	SCV002019988	pathogenic	Chromosome 2q32-q33 deletion syndrome	2020-02-21	criteria provided, single submitter	clinical testing
OMIM	RCV000002627	SCV000022785	pathogenic	Chromosome 2q32-q33 deletion syndrome	2013-12-04	no assertion criteria provided	literature only
GeneReviews	RCV000002627	SCV000837665	not provided	Chromosome 2q32-q33 deletion syndrome		no assertion provided	literature only
Autoinflammatory diseases unit, CHU de Montpellier	RCV001261363	SCV001438238	pathogenic	Cleft palate	2017-01-23	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000256175	SCV001742494	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000256175	SCV001959050	pathogenic	not provided		no assertion criteria provided	clinical testing