Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1
The NM_031885.5(BBS2):āc.367A>Gā(p.Ile123Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,704 control chromosomes in the GnomAD database, including 30,666 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
BBS2 (HGNC:967): (Bardet-Biedl syndrome 2) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene forms a multiprotein BBSome complex with seven other BBS proteins.[provided by RefSeq, Oct 2014]
Computational evidence support a benign effect (MetaRNN=0.0039009154).
BP6
Variant 16-56511263-T-C is Benign according to our data. Variant chr16-56511263-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 261981.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=9}. Variant chr16-56511263-T-C is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.
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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter
clinical testing
Athena Diagnostics
Jun 02, 2017
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Benign, no assertion criteria provided
clinical testing
Natera, Inc.
Sep 16, 2020
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Benign, criteria provided, single submitter
clinical testing
Genome-Nilou Lab
Jun 10, 2021
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not specified Benign:2
Benign, no assertion criteria provided
clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
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Benign, criteria provided, single submitter
clinical testing
PreventionGenetics, part of Exact Sciences
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Bardet-Biedl syndrome 1 Benign:2
Benign, criteria provided, single submitter
clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Sep 21, 2015
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Benign, no assertion criteria provided
clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
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not provided Benign:2
Benign, criteria provided, single submitter
not provided
Breakthrough Genomics, Breakthrough Genomics
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Benign, criteria provided, single submitter
clinical testing
GeneDx
Nov 10, 2018
This variant is associated with the following publications: (PMID: 24746959, 20498079, 24400638) -
Retinal dystrophy Uncertain:1
Uncertain significance, criteria provided, single submitter