rs1018314879

Positions:

• chr16-56501455-C-G
• chr16-56501455-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_031885.5(BBS2):​c.1123G>C​(p.Gly375Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: BBS2 NM_031885.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 7.31

Genes affected

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS2	NM_031885.5	c.1123G>C	p.Gly375Arg	missense_variant	10/17	ENST00000245157.11	NP_114091.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS2	ENST00000245157.11	c.1123G>C	p.Gly375Arg	missense_variant	10/17	1	NM_031885.5	ENSP00000245157	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

research

Gharavi Laboratory, Columbia University

Sep 16, 2018

- -

Bardet-Biedl syndrome 2;C4225281:Retinitis pigmentosa 74 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 28, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.69	D;.
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D;.
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Pathogenic	0.87	D
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Vest4		0.78
MutPred		0.56		Gain of solvent accessibility (P = 0.0171);Gain of solvent accessibility (P = 0.0171);
MVP		0.93
MPC		0.96
ClinPred		0.99	D
GERP RS		5.4
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1018314879; hg19: chr16-56535367;