Submissions for variant NM_001172509.2(SATB2):c.1375C>T (p.Arg459Ter)

dbSNP: rs1553547838

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625170	SCV000743993	pathogenic	Isolated cleft palate	2017-07-28	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000625170	SCV000745950	pathogenic	Isolated cleft palate	2014-10-24	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000680089	SCV000807529	pathogenic	Chromosome 2q32-q33 deletion syndrome	2017-09-01	criteria provided, single submitter	clinical testing	This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory de novo in a set of 10-year-old male twins with intellectual disability, dysmorphisms, cleft palate, hyperextensibility
Ambry Genetics	RCV002317378	SCV000850482	pathogenic	Inborn genetic diseases	2017-03-03	criteria provided, single submitter	clinical testing	The p.R459* pathogenic mutation (also known as c.1375C>T), located in coding exon 7 of the SATB2 gene, results from a C to T substitution at nucleotide position 1375. This changes the amino acid from an arginine to a stop codon within coding exon 7. This mutation occurred de novo in two patients with developmental delay and cleft palate (Deciphering Developmental Disorders Study. Nature, 2015 Mar;519:223-8; Lee JS et al. Clin. Genet., 2016 Jun;89:728-32). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Fulgent Genetics, Fulgent Genetics	RCV000680089	SCV000894250	pathogenic	Chromosome 2q32-q33 deletion syndrome	2018-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001564846	SCV001788074	pathogenic	not provided	2023-10-05	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; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28211976, 32446642, 25533962, 28135719, 29436146, 28191890, 26596517, 25326635, 32581362, 31785789)
Invitae	RCV000680089	SCV003524888	pathogenic	Chromosome 2q32-q33 deletion syndrome	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg459*) 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 individual(s) with Glass syndrome (PMID: 26596517, 28211976). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 522269). For these reasons, this variant has been classified as Pathogenic.
3billion	RCV000680089	SCV003841999	pathogenic	Chromosome 2q32-q33 deletion syndrome	2023-02-23	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. It has been previously reported as de novo in at least two similarly affected unrelated individuals (PMID: 25533962, 28151491). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes	RCV003389057	SCV004101204	pathogenic	Neurodevelopmental disorder	2022-08-29	criteria provided, single submitter	clinical testing
GeneReviews	RCV000680089	SCV000837673	not provided	Chromosome 2q32-q33 deletion syndrome		no assertion provided	literature only
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003958	SCV001161949	likely pathogenic	Dystonic disorder; Intellectual disability		no assertion criteria provided	research
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001564846	SCV001953050	pathogenic	not provided		no assertion criteria provided	clinical testing