chr16-56514589-C-T

Position:

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B: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]

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 (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/exons	MANE	Protein	UniProt
BBS2	NM_031885.5 linkuse as main transcript	c.209G>A	p.Ser70Asn	missense_variant	2/17	ENST00000245157.11	NP_114091.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BBS2	ENST00000245157.11 linkuse as main transcript	c.209G>A	p.Ser70Asn	missense_variant	2/17	1	NM_031885.5	ENSP00000245157	P1

Frequencies

GnomAD3 genomes

AF:

0.995

AC:

151493

AN:

152224

Hom.:

75385

Cov.:

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.:

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.:

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: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 15, 2016	- -

Bardet-Biedl syndrome 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 16, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 26, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Retinitis pigmentosa 74

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Retinal dystrophy

Benign:1

Benign, criteria provided, single submitter

research

Dept Of Ophthalmology, Nagoya University

Oct 01, 2023

- -

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

0.057

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.31

DEOGEN2

Benign

0.23

T;.

Eigen

Benign

-0.085

Eigen_PC

Benign

0.026

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.39

T;.

MetaRNN

Benign

6.9e-7

T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

P;P

PrimateAI

Uncertain

0.70

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

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.

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