Submissions for variant NM_024649.5(BBS1):c.1570_1572del (p.Asn524del)

dbSNP: rs863224782

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000198771	SCV004021211	likely pathogenic	Bardet-Biedl syndrome	2023-06-26	criteria provided, single submitter	clinical testing	Variant summary: BBS1 c.1570_1572delAAC (p.Asn524del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 4e-06 in 251490 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1570_1572delAAC has been reported in the literature in both compound heterozygous and homozygous individuals affected with features of Bardet-Biedl Syndrome (e.g., Gerth_2008, Deveault_2011, Forsythe_2017, Saeed_2020, Weisschuh_2020, Nasser_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 21344540, 27659767, 17980398, 35886001, 32349990, 32531858). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics	RCV001542479	SCV004217370	likely pathogenic	Bardet-Biedl syndrome 1	2023-08-18	criteria provided, single submitter	clinical testing
Invitae	RCV000198771	SCV000255071	uncertain significance	Bardet-Biedl syndrome	2021-09-24	flagged submission	clinical testing	This variant, c.1570_1572del, results in the deletion of 1 amino acid(s) of the BBS1 protein (p.Asn524del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Bardet-Biedl syndrome (PMID: 21344540, 32349990). ClinVar contains an entry for this variant (Variation ID: 216741). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genomics England Pilot Project, Genomics England	RCV001542479	SCV001760276	pathogenic	Bardet-Biedl syndrome 1		no assertion criteria provided	clinical testing