rs115078074

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.-40T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 1,553,382 control chromosomes in the GnomAD database, including 3,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 671 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2712 hom. )

Consequence

BBS2
NM_031885.5 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0260

Publications

8 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 (BayesDel_noAF=-0.87).

BP6

Variant 16-56519902-A-G is Benign according to our data. Variant chr16-56519902-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 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	Effect	Exon Rank	Protein	UniProt
BBS2	NM_031885.5	MANE Select	c.-40T>C	5_prime_UTR	Exon 1 of 17	NP_114091.4
BBS2	NM_001377456.1		c.-40T>C	5_prime_UTR	Exon 1 of 18	NP_001364385.1	Q9BXC9
BBS2	NR_165293.1		n.123T>C	non_coding_transcript_exon	Exon 1 of 17

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BBS2	ENST00000245157.11	TSL:1 MANE Select	c.-40T>C	5_prime_UTR	Exon 1 of 17	ENSP00000245157.5	Q9BXC9
BBS2	ENST00000565781.6	TSL:1	n.131+55T>C	intron	N/A
BBS2	ENST00000682188.1		c.-40T>C	5_prime_UTR	Exon 1 of 17	ENSP00000507655.1	A0A804HJV0

Frequencies

GnomAD3 genomes

AF:

0.0774

AC:

11781

AN:

152142

Hom.:

666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0494

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0507

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0417

Gnomad OTH

AF:

0.0684

GnomAD2 exomes

AF:

0.0684

AC:

16694

AN:

244210

AF XY:

0.0696

show subpopulations

Gnomad AFR exome

AF:

0.143

Gnomad AMR exome

AF:

0.0521

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.167

Gnomad FIN exome

AF:

0.0440

Gnomad NFE exome

AF:

0.0398

Gnomad OTH exome

AF:

0.0587

GnomAD4 exome

AF:

0.0507

AC:

71072

AN:

1401122

Hom.:

2712

Cov.:

AF XY:

0.0526

AC XY:

36789

AN XY:

700044

show subpopulations

African (AFR)

AF:

0.147

AC:

4723

AN:

32112

American (AMR)

AF:

0.0498

AC:

2212

AN:

44406

Ashkenazi Jewish (ASJ)

AF:

0.0198

AC:

508

AN:

25692

East Asian (EAS)

AF:

0.121

AC:

4741

AN:

39274

South Asian (SAS)

AF:

0.126

AC:

10649

AN:

84732

European-Finnish (FIN)

AF:

0.0441

AC:

2335

AN:

52938

Middle Eastern (MID)

AF:

0.0468

AC:

265

AN:

5658

European-Non Finnish (NFE)

AF:

0.0398

AC:

42073

AN:

1058018

Other (OTH)

AF:

0.0612

AC:

3566

AN:

58292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

3054

6108

9162

12216

15270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1714

3428

5142

6856

8570

<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:

0.0775

AC:

11806

AN:

152260

Hom.:

671

Cov.:

AF XY:

0.0791

AC XY:

5885

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.144

AC:

5998

AN:

41550

American (AMR)

AF:

0.0494

AC:

756

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3472

East Asian (EAS)

AF:

0.153

AC:

793

AN:

5170

South Asian (SAS)

AF:

0.135

AC:

652

AN:

4820

European-Finnish (FIN)

AF:

0.0507

AC:

538

AN:

10612

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0417

AC:

2839

AN:

68006

Other (OTH)

AF:

0.0705

AC:

149

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

565

1129

1694

2258

2823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0584

Hom.:

Bravo

AF:

0.0793

Asia WGS

AF:

0.165

AC:

574

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Bardet-Biedl syndrome 2 (2)

not provided (2)

not specified (1)

Retinitis pigmentosa 74 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.0

(source)

DANN

Benign

0.50

PhyloP100

0.026

PromoterAI

0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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