Submissions for variant NM_031885.5(BBS2):c.118G>T (p.Val40Phe)

gnomAD frequency: 0.00002  dbSNP: rs886043059

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725618	SCV000338210	likely pathogenic	not provided	2016-03-18	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001075302	SCV001240919	uncertain significance	Retinal dystrophy	2017-12-22	criteria provided, single submitter	clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000305383	SCV001443724	likely pathogenic	Bardet-Biedl syndrome 2	2019-10-23	criteria provided, single submitter	clinical testing	This variant has been previously reported as a change in patient with retinal disease (PMID: 28559085). It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.118G>T (p.Val40Phe) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Based on the available evidence, the c.118G>T (p.Val40Phe) variant is classified as Likely Pathogenic.
Myriad Genetics, Inc.	RCV000305383	SCV002060203	uncertain significance	Bardet-Biedl syndrome 2	2021-11-03	criteria provided, single submitter	clinical testing	NM_031885.3(BBS2):c.118G>T(V40F) is a missense variant classified as a variant of uncertain significance in the context of Bardet-Biedl syndrome, BBS2-related. V40F has been observed in cases with relevant disease (PMID: 28559085). Functional assessments of this variant are not available in the literature. V40F has not been observed in population frequency databases. In summary, there is insufficient evidence to classify NM_031885.3(BBS2):c.118G>T(V40F) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.
3billion	RCV002250616	SCV002521059	uncertain significance	Retinitis pigmentosa 74	2022-05-22	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.88; 3Cnet: 3CNET). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with BBS2 related disorder (ClinVar ID: VCV000285263 / PMID: 28559085). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline.
Invitae	RCV002519177	SCV003443338	uncertain significance	Bardet-Biedl syndrome	2022-08-05	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 40 of the BBS2 protein (p.Val40Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 28559085). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 285263). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Baylor Genetics	RCV000305383	SCV004214003	likely pathogenic	Bardet-Biedl syndrome 2	2024-02-02	criteria provided, single submitter	clinical testing