chr16-56511263-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/19 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

Publications

39 publications found

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 Gene-Disease associations (from GenCC):

Bardet-Biedl syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
BBS2-related ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
retinitis pigmentosa 74
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

BBS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 261981.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031885.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBS2	NM_031885.5	MANE Select	c.367A>G	p.Ile123Val	missense	Exon 3 of 17	NP_114091.4
BBS2	NM_001377456.1		c.367A>G	p.Ile123Val	missense	Exon 3 of 18	NP_001364385.1	Q9BXC9
BBS2	NR_165293.1		n.529A>G		non_coding_transcript_exon	Exon 3 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBS2	ENST00000245157.11	TSL:1 MANE Select	c.367A>G	p.Ile123Val	missense	Exon 3 of 17	ENSP00000245157.5	Q9BXC9
BBS2	ENST00000565781.6	TSL:1	n.381A>G		non_coding_transcript_exon	Exon 3 of 12
BBS2	ENST00000682188.1		c.367A>G	p.Ile123Val	missense	Exon 3 of 17	ENSP00000507655.1	A0A804HJV0

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

GnomAD2 exomes

AF:

0.215

AC:

53946

AN:

251270

AF XY:

0.208

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 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

African (AFR)

AF:

0.230

AC:

7688

AN:

33470

American (AMR)

AF:

0.286

AC:

12799

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

5539

AN:

26134

East Asian (EAS)

AF:

0.411

AC:

16308

AN:

39690

South Asian (SAS)

AF:

0.188

AC:

16233

AN:

86256

European-Finnish (FIN)

AF:

0.174

AC:

9258

AN:

53354

Middle Eastern (MID)

AF:

0.150

AC:

868

AN:

5768

European-Non Finnish (NFE)

AF:

0.173

AC:

192518

AN:

1111850

Other (OTH)

AF:

0.198

AC:

11970

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

12919

25838

38758

51677

64596

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7080

14160

21240

28320

35400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.207

AC:

31502

AN:

152068

Hom.:

3450

Cov.:

AF XY:

0.208

AC XY:

15431

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.232

AC:

9618

AN:

41470

American (AMR)

AF:

0.242

AC:

3695

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

709

AN:

3468

East Asian (EAS)

AF:

0.400

AC:

2065

AN:

5162

South Asian (SAS)

AF:

0.192

AC:

927

AN:

4822

European-Finnish (FIN)

AF:

0.184

AC:

1943

AN:

10576

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11967

AN:

67972

Other (OTH)

AF:

0.211

AC:

445

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1272

2544

3816

5088

6360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.189

Hom.:

13216

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

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bardet-Biedl syndrome 2 (4)

Bardet-Biedl syndrome 1 (2)

not provided (2)

not specified (2)

Bardet-Biedl syndrome (1)

Retinal dystrophy (1)

Retinitis pigmentosa 74 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.0

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.22

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.65

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0039

MetaSVM

Benign

-1.0

PhyloP100

0.40

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.24

REVEL

Benign

0.17

Sift

Benign

0.56

Sift4G

Benign

0.54

Vest4

0.056

MPC

0.21

ClinPred

0.0022

GERP RS

0.54

gMVP

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over