Submissions for variant NM_001017420.3(ESCO2):c.1132-7A>G

gnomAD frequency: 0.00007  dbSNP: rs80359862

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000020396	SCV000193109	pathogenic	Roberts-SC phocomelia syndrome	2013-02-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000519470	SCV000617528	uncertain significance	not provided	2019-07-22	criteria provided, single submitter	clinical testing	In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 16380922, 18411254)
Invitae	RCV000519470	SCV000957265	pathogenic	not provided	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change falls in intron 6 of the ESCO2 gene. It does not directly change the encoded amino acid sequence of the ESCO2 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs80359862, gnomAD 0.006%). This variant has been observed in individual(s) with Roberts syndrome (PMID: 16380922, 30508616). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 21234). Studies have shown that this variant results in a 6-nucleotide insertion and introduces a premature termination codon (PMID: 16380922). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000020396	SCV001521735	pathogenic	Roberts-SC phocomelia syndrome	2019-11-13	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Revvity Omics, Revvity	RCV000519470	SCV002022210	pathogenic	not provided	2020-11-25	criteria provided, single submitter	clinical testing
GeneReviews	RCV000020396	SCV000040791	not provided	Roberts-SC phocomelia syndrome		no assertion provided	literature only
Natera, Inc.	RCV000020396	SCV001460457	likely pathogenic	Roberts-SC phocomelia syndrome	2020-09-16	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000519470	SCV001929048	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000519470	SCV001955225	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000519470	SCV002038433	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	RCV000020396	SCV003927894	likely pathogenic	Roberts-SC phocomelia syndrome	2023-04-01	no assertion criteria provided	clinical testing