16-56514589-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S70I) has been classified as Uncertain significance.

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 P:1B:13

Conservation

PhyloP100: 4.99

Publications

57 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 -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 VariationId is 285261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 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.209G>A	p.Ser70Asn	missense	Exon 2 of 17	NP_114091.4
BBS2	NM_001377456.1		c.209G>A	p.Ser70Asn	missense	Exon 2 of 18	NP_001364385.1	Q9BXC9
BBS2	NR_165293.1		n.371G>A		non_coding_transcript_exon	Exon 2 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BBS2	ENST00000245157.11	TSL:1 MANE Select	c.209G>A	p.Ser70Asn	missense	Exon 2 of 17	ENSP00000245157.5	Q9BXC9
BBS2	ENST00000565781.6	TSL:1	n.223G>A		non_coding_transcript_exon	Exon 2 of 12
BBS2	ENST00000682188.1		c.209G>A	p.Ser70Asn	missense	Exon 2 of 17	ENSP00000507655.1	A0A804HJV0

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

GnomAD2 exomes

AF:

0.994

AC:

249946

AN:

251430

AF XY:

0.994

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 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

African (AFR)

AF:

0.999

AC:

33449

AN:

33480

American (AMR)

AF:

0.996

AC:

44552

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.995

AC:

26001

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39698

AN:

39698

South Asian (SAS)

AF:

0.990

AC:

85365

AN:

86256

European-Finnish (FIN)

AF:

0.999

AC:

53382

AN:

53420

Middle Eastern (MID)

AF:

0.986

AC:

5688

AN:

5768

European-Non Finnish (NFE)

AF:

0.993

AC:

1103818

AN:

1111980

Other (OTH)

AF:

0.994

AC:

60035

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

540

1081

1621

2162

2702

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21668

43336

65004

86672

108340

<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:

0.995

AC:

151611

AN:

152342

Hom.:

75444

Cov.:

AF XY:

0.995

AC XY:

74130

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.998

AC:

41495

AN:

41562

American (AMR)

AF:

0.993

AC:

15197

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.995

AC:

3455

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5182

AN:

5182

South Asian (SAS)

AF:

0.991

AC:

4784

AN:

4828

European-Finnish (FIN)

AF:

1.00

AC:

10622

AN:

10626

Middle Eastern (MID)

AF:

0.986

AC:

290

AN:

294

European-Non Finnish (NFE)

AF:

0.993

AC:

67568

AN:

68044

Other (OTH)

AF:

0.995

AC:

2106

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.993

Hom.:

169784

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Bardet-Biedl syndrome 2 (3)

not provided (2)

Retinal dystrophy (2)

Bardet-Biedl syndrome (1)

Retinitis pigmentosa 74 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.23

Eigen

Benign

-0.085

Eigen_PC

Benign

0.026

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.39

MetaRNN

Benign

6.9e-7

MetaSVM

Benign

-0.91

PhyloP100

5.0

PrimateAI

Uncertain

0.70

PROVEAN

Benign

2.8

REVEL

Benign

0.27

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.077

MPC

0.23

ClinPred

0.0061

GERP RS

5.5

gMVP

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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