Submissions for variant NM_003193.5(TBCE):c.155_166del (p.Ser52_Gly55del)

dbSNP: rs767004810

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224858	SCV000280889	pathogenic	not provided	2014-12-18	criteria provided, single submitter	clinical testing
Centre for Translational Omics - GOSgene, University College London	RCV000005608	SCV000778576	likely pathogenic	Hypoparathyroidism-retardation-dysmorphism syndrome	2018-03-16	criteria provided, single submitter	clinical testing
Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University	RCV000005608	SCV000891681	pathogenic	Hypoparathyroidism-retardation-dysmorphism syndrome	2017-12-30	criteria provided, single submitter	clinical testing
Pathology and Clinical Laboratory Medicine, King Fahad Medical City	RCV000005608	SCV000996294	pathogenic	Hypoparathyroidism-retardation-dysmorphism syndrome		criteria provided, single submitter	clinical testing
GeneDx	RCV000224858	SCV001820079	pathogenic	not provided	2020-01-29	criteria provided, single submitter	clinical testing	In-frame deletion of 4 amino acids in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31589614, 26231322, 30638765, 30049826, 25097779, 12389028, 26336027, 20152369, 30080992, 29620724)
Revvity Omics, Revvity	RCV000224858	SCV002018933	pathogenic	not provided	2022-01-18	criteria provided, single submitter	clinical testing
Centogene AG - the Rare Disease Company	RCV000005608	SCV002028329	pathogenic	Hypoparathyroidism-retardation-dysmorphism syndrome	2021-07-20	criteria provided, single submitter	clinical testing
3billion	RCV000005608	SCV002521836	pathogenic	Hypoparathyroidism-retardation-dysmorphism syndrome	2022-05-22	criteria provided, single submitter	clinical testing	The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). Inframe deletion located in a nonrepeat region: predicted to change the length of the protein and disrupt normal protein function. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID:12389028). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID:12389028, 20152369, 25097779, 26231322, 26336027, 30080992, 30638765). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Invitae	RCV000224858	SCV003524137	pathogenic	not provided	2023-01-13	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 5290). This variant has been observed in individuals with hypoparathyroidism-retardation-dysmorphism syndrome (PMID: 12389028, 20152369, 26231322, 30080992). It is commonly reported in individuals of Middle Eastern ancestry (PMID: 12389028, 30080992). This variant is present in population databases (rs767004810, gnomAD 0.006%). This variant, c.155_166del, results in the deletion of 4 amino acid(s) of the TBCE protein (p.Ser52_Gly55del), but otherwise preserves the integrity of the reading frame.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV003989279	SCV004805967	pathogenic	Encephalopathy, progressive, with amyotrophy and optic atrophy	2024-03-25	criteria provided, single submitter	clinical testing
OMIM	RCV000005608	SCV000025790	pathogenic	Hypoparathyroidism-retardation-dysmorphism syndrome	2002-11-01	no assertion criteria provided	literature only
OMIM	RCV000191990	SCV000246253	pathogenic	Autosomal recessive Kenny-Caffey syndrome	2002-11-01	no assertion criteria provided	literature only
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City	RCV000005608	SCV001190740	pathogenic	Hypoparathyroidism-retardation-dysmorphism syndrome	2020-02-05	no assertion criteria provided	clinical testing
Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	RCV000005608	SCV003927852	pathogenic	Hypoparathyroidism-retardation-dysmorphism syndrome	2023-04-01	no assertion criteria provided	clinical testing