Submissions for variant NM_031885.5(BBS2):c.327G>A (p.Ser109=)

gnomAD frequency: 0.00001  dbSNP: rs770497817

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000667692	SCV000398072	uncertain significance	Bardet-Biedl syndrome 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Counsyl	RCV000667692	SCV000792182	likely benign	Bardet-Biedl syndrome 2	2017-06-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001239194	SCV001412046	likely benign	Bardet-Biedl syndrome	2024-01-20	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV000667692	SCV005044793	uncertain significance	Bardet-Biedl syndrome 2		criteria provided, single submitter	clinical testing	The synonymous c.327G>A p.Ser109 variant in BBS2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Ser109 variant has allele frequency 0.002% in gnomAD Exomes and is novel not in any individuals in 1000 Genomes. This variant has been reported to the ClinVar database as Likely benign / Uncertain Significance. This p.Ser109 type of mutation causes no change in the protein that is produced, which is why it's considered as synonymous mutation. For these reasons, this variant has been classified as Variant of Uncertain Significance VUS.
Natera, Inc.	RCV000667692	SCV001464857	uncertain significance	Bardet-Biedl syndrome 2	2020-05-28	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004732847	SCV005355352	likely benign	BBS2-related disorder	2024-03-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).