rs78076550

Positions:

chr16-56519904-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031885.5(BBS2):c.-42T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 1,546,074 control chromosomes in the GnomAD database, including 3,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 672 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2694 hom. )

Consequence

BBS2
NM_031885.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.44

Variant links:

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]

BBS2 links:

BBS2 (HGNC:):

BBS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 16-56519904-A-C is Benign according to our data. Variant chr16-56519904-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 261978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56519904-A-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS2	NM_031885.5 linkuse as main transcript	c.-42T>G		5_prime_UTR_premature_start_codon_gain_variant	1/17	ENST00000245157.11	NP_114091.4	Q9BXC9
BBS2	NM_031885.5 linkuse as main transcript	c.-42T>G		5_prime_UTR_variant	1/17	ENST00000245157.11	NP_114091.4	Q9BXC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS2	ENST00000245157.11 linkuse as main transcript	c.-42T>G		5_prime_UTR_premature_start_codon_gain_variant	1/17	1	NM_031885.5	ENSP00000245157.5		Q9BXC9
BBS2	ENST00000245157.11 linkuse as main transcript	c.-42T>G		5_prime_UTR_variant	1/17	1	NM_031885.5	ENSP00000245157.5		Q9BXC9

Frequencies

GnomAD3 genomes

AF:

0.0774

AC:

11783

AN:

152156

Hom.:

667

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0495

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0507

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0417

Gnomad OTH

AF:

0.0684

GnomAD3 exomes

AF:

0.0683

AC:

16622

AN:

243496

Hom.:

859

AF XY:

0.0695

AC XY:

9200

AN XY:

132344

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.0521

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.129

Gnomad FIN exome

AF:

0.0436

Gnomad NFE exome

AF:

0.0396

Gnomad OTH exome

AF:

0.0588

GnomAD4 exome

AF:

0.0508

AC:

70738

AN:

1393800

Hom.:

2694

Cov.:

AF XY:

0.0526

AC XY:

36627

AN XY:

696708

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.0498

Gnomad4 ASJ exome

AF:

0.0198

Gnomad4 EAS exome

AF:

0.121

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.0440

Gnomad4 NFE exome

AF:

0.0398

Gnomad4 OTH exome

AF:

0.0611

GnomAD4 genome

AF:

0.0775

AC:

11808

AN:

152274

Hom.:

672

Cov.:

AF XY:

0.0791

AC XY:

5886

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.144

Gnomad4 AMR

AF:

0.0494

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.153

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.0507

Gnomad4 NFE

AF:

0.0418

Gnomad4 OTH

AF:

0.0705

Alfa

AF:

0.0555

Hom.:

Bravo

AF:

0.0793

Asia WGS

AF:

0.165

AC:

574

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Retinitis pigmentosa 74

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

DANN

Benign

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over