Submissions for variant NM_024685.4(BBS10):c.728_731del (p.Lys243fs)

dbSNP: rs786204671

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169474	SCV000220920	likely pathogenic	Bardet-Biedl syndrome 10	2014-11-25	criteria provided, single submitter	literature only
Labcorp Genetics (formerly Invitae), Labcorp	RCV000638365	SCV000759864	pathogenic	Bardet-Biedl syndrome	2023-10-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys243Ilefs*15) in the BBS10 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 481 amino acid(s) of the BBS10 protein. This variant is present in population databases (rs786204671, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 16582908, 17106446, 22353939, 22773737, 24041679, 27245532). It is commonly reported in individuals of South African ancestry (PMID: 16582908, 17106446, 22353939, 22773737, 24041679, 27245532). This variant is also known as c.995_999delAAGA (p.Q242fs258X). ClinVar contains an entry for this variant (Variation ID: 189071). This variant disrupts a region of the BBS10 protein in which other variant(s) (p.Gly677Valfs*5, p.Val707*) have been determined to be pathogenic (PMID: 20472660, 22773737, 25982971, 27486776; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000169474	SCV001752436	pathogenic	Bardet-Biedl syndrome 10	2021-06-30	criteria provided, single submitter	clinical testing
3billion, Medical Genetics	RCV000169474	SCV002058552	pathogenic	Bardet-Biedl syndrome 10	2022-01-03	criteria provided, single submitter	clinical testing	Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_S). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000189071, PMID:16582908). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV000169474	SCV003807890	pathogenic	Bardet-Biedl syndrome 10	2022-09-16	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1 strong, PS4 moderated, PM2 moderated, PM3 moderated
Division of Human Genetics, National Health Laboratory Service/University of the Witwatersrand	RCV000638365	SCV004123099	pathogenic	Bardet-Biedl syndrome	2023-07-01	criteria provided, single submitter	research
Baylor Genetics	RCV000169474	SCV004217450	pathogenic	Bardet-Biedl syndrome 10	2023-06-09	criteria provided, single submitter	clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000169474	SCV004808170	pathogenic	Bardet-Biedl syndrome 10	2024-03-29	criteria provided, single submitter	clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences	RCV000169474	SCV005044663	pathogenic	Bardet-Biedl syndrome 10	2024-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV004719733	SCV005325125	pathogenic	not provided	2023-09-06	criteria provided, single submitter	clinical testing	Reported as the most common pathogenic variant among individuals with BBS10-related ciliopathy in South Africa (Fieggen et al., 2016); Frameshift variant predicted to result in protein truncation, as the last 481 amino acids are replaced with 14 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 32949114, 30614526, 27486776, 25982971, 31964843, 27245532, 24041679, 20472660, 17106446, 22773737, 25780760, 22353939, 16582908)
Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University	RCV000638365	SCV000839564	pathogenic	Bardet-Biedl syndrome	2018-09-15	no assertion criteria provided	provider interpretation
Natera, Inc.	RCV000169474	SCV002091783	pathogenic	Bardet-Biedl syndrome 10	2021-09-16	no assertion criteria provided	clinical testing
Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	RCV000169474	SCV003927959	pathogenic	Bardet-Biedl syndrome 10	2023-04-01	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004739550	SCV005361718	pathogenic	BBS10-related disorder	2024-08-29	no assertion criteria provided	clinical testing	The BBS10 c.728_731delAAGA variant is predicted to result in a frameshift and premature protein termination (p.Lys243Ilefs*15). This variant was reported in the homozygous state in at least fifty individuals with Bardet-Biedl syndrome, and is a suggested founder mutation in the South African population (Fieggen K et al 2016. PubMed ID: 27245532). This variant has not been reported in a large population database, indicating this variant is rare. Frameshift variants in BBS10 are expected to be pathogenic. This variant is interpreted as pathogenic.