chr16-56514589-C-T

Variant summary

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

The NM_031885.5(BBS2):​c.209G>A​(p.Ser70Asn) variant causes a missense change. The variant allele was found at a frequency of 0.993 in 1,614,200 control chromosomes in the GnomAD database, including 796,560 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75444 hom., cov: 31)
Exomes 𝑓: 0.99 ( 721116 hom. )

Consequence

BBS2
NM_031885.5 missense

Scores

1
16

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:13

Conservation

PhyloP100: 4.99
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]

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 (MetaRNN=6.8563224E-7).
BP6
Variant 16-56514589-C-T is Benign according to our data. Variant chr16-56514589-C-T is described in ClinVar as [Benign]. Clinvar id is 285261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56514589-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BBS2NM_031885.5 linkc.209G>A p.Ser70Asn missense_variant Exon 2 of 17 ENST00000245157.11 NP_114091.4 Q9BXC9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BBS2ENST00000245157.11 linkc.209G>A p.Ser70Asn missense_variant Exon 2 of 17 1 NM_031885.5 ENSP00000245157.5 Q9BXC9

Frequencies

GnomAD3 genomes
AF:
0.995
AC:
151493
AN:
152224
Hom.:
75385
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.998
Gnomad AMI
AF:
1.00
Gnomad AMR
AF:
0.993
Gnomad ASJ
AF:
0.995
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
0.991
Gnomad FIN
AF:
1.00
Gnomad MID
AF:
0.987
Gnomad NFE
AF:
0.993
Gnomad OTH
AF:
0.995
GnomAD3 exomes
AF:
0.994
AC:
249946
AN:
251430
Hom.:
124238
AF XY:
0.994
AC XY:
135025
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.998
Gnomad AMR exome
AF:
0.996
Gnomad ASJ exome
AF:
0.995
Gnomad EAS exome
AF:
1.00
Gnomad SAS exome
AF:
0.990
Gnomad FIN exome
AF:
1.00
Gnomad NFE exome
AF:
0.992
Gnomad OTH exome
AF:
0.991
GnomAD4 exome
AF:
0.993
AC:
1451988
AN:
1461858
Hom.:
721116
Cov.:
53
AF XY:
0.993
AC XY:
722103
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.999
Gnomad4 AMR exome
AF:
0.996
Gnomad4 ASJ exome
AF:
0.995
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
0.990
Gnomad4 FIN exome
AF:
0.999
Gnomad4 NFE exome
AF:
0.993
Gnomad4 OTH exome
AF:
0.994
GnomAD4 genome
AF:
0.995
AC:
151611
AN:
152342
Hom.:
75444
Cov.:
31
AF XY:
0.995
AC XY:
74130
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.998
Gnomad4 AMR
AF:
0.993
Gnomad4 ASJ
AF:
0.995
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
0.991
Gnomad4 FIN
AF:
1.00
Gnomad4 NFE
AF:
0.993
Gnomad4 OTH
AF:
0.995
Alfa
AF:
0.993
Hom.:
123316
Bravo
AF:
0.995
TwinsUK
AF:
0.993
AC:
3682
ALSPAC
AF:
0.992
AC:
3825
ESP6500AA
AF:
0.999
AC:
4390
ESP6500EA
AF:
0.992
AC:
8534
ExAC
AF:
0.994
AC:
120656
Asia WGS
AF:
0.997
AC:
3468
AN:
3478
EpiCase
AF:
0.992
EpiControl
AF:
0.992

ClinVar

Significance: Benign
Submissions summary: Pathogenic:1Benign:13
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
-
Genome Diagnostics Laboratory, University Medical Center Utrecht
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Nov 15, 2016
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Bardet-Biedl syndrome 2 Benign:3
Jul 14, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

May 28, 2019
Mendelics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Nov 16, 2019
Natera, Inc.
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Retinal dystrophy Pathogenic:1Benign:1
Oct 01, 2023
Dept Of Ophthalmology, Nagoya University
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: research

- -

Jan 01, 2013
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg
Significance: Likely pathogenic
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Sep 26, 2017
Athena Diagnostics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Retinitis pigmentosa 74 Benign:1
Jul 14, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Bardet-Biedl syndrome Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.057
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
18
DANN
Benign
0.31
DEOGEN2
Benign
0.23
T;.
Eigen
Benign
-0.085
Eigen_PC
Benign
0.026
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.39
T;.
MetaRNN
Benign
6.9e-7
T;T
MetaSVM
Benign
-0.91
T
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
2.8
N;N
REVEL
Benign
0.27
Sift
Benign
1.0
T;T
Sift4G
Benign
1.0
T;T
Vest4
0.077
MPC
0.23
ClinPred
0.0061
T
GERP RS
5.5
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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.

Other links and lift over

dbSNP: rs4784677; hg19: chr16-56548501; API