chr16-56511263-T-C

Position:

chr16-56511263-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_031885.5(BBS2):c.367A>G(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).

Frequency

Genomes: 𝑓 0.21 ( 3450 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27216 hom. )

Consequence

BBS2
NM_031885.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:12

Conservation

PhyloP100: 0.398

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BBS2	NM_031885.5 link	c.367A>G	p.Ile123Val	missense_variant	3/17	ENST00000245157.11	NP_114091.4	Q9BXC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS2	ENST00000245157.11 link	c.367A>G	p.Ile123Val	missense_variant	3/17	1	NM_031885.5	ENSP00000245157.5		Q9BXC9

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31484

AN:

151950

Hom.:

3447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.401

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.215

AC:

53946

AN:

251270

Hom.:

6419

AF XY:

0.208

AC XY:

28251

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.232

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.405

Gnomad SAS exome

AF:

0.193

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.171

Gnomad OTH exome

AF:

0.205

GnomAD4 exome

AF:

0.187

AC:

273181

AN:

1461636

Hom.:

27216

Cov.:

AF XY:

0.186

AC XY:

135218

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.230

Gnomad4 AMR exome

AF:

0.286

Gnomad4 ASJ exome

AF:

0.212

Gnomad4 EAS exome

AF:

0.411

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.173

Gnomad4 OTH exome

AF:

0.198

GnomAD4 genome

AF:

0.207

AC:

31502

AN:

152068

Hom.:

3450

Cov.:

AF XY:

0.208

AC XY:

15431

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.232

Gnomad4 AMR

AF:

0.242

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.400

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.176

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.185

Hom.:

6796

Bravo

AF:

0.216

TwinsUK

AF:

0.166

AC:

614

ALSPAC

AF:

0.178

AC:

685

ESP6500AA

AF:

0.226

AC:

994

ESP6500EA

AF:

0.180

AC:

1546

ExAC

AF:

0.209

AC:

25369

Asia WGS

AF:

0.296

AC:

1028

AN:

3478

EpiCase

AF:

0.172

EpiControl

AF:

0.172

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:12

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Bardet-Biedl syndrome 2

Benign:4

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jun 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 02, 2017	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 24746959, 20498079, 24400638) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Retinal dystrophy

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

Retinitis pigmentosa 74

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Bardet-Biedl syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.0

DANN

Benign

0.60

DEOGEN2

Benign

0.22

T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.65

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.76

T;.

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.24

N;N

REVEL

Benign

0.17

Sift

Benign

0.56

T;T

Sift4G

Benign

0.54

T;T

Vest4

0.056

MPC

0.21

ClinPred

0.0022

GERP RS

0.54

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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