rs78076550

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.-42T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 1,546,074 control chromosomes in the GnomAD database, including 3,366 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 ( 672 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2694 hom. )

Consequence

BBS2
NM_031885.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.44

Publications

7 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: Genomics England PanelApp, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health
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=-0.89).

BP6

Variant 16-56519904-A-C is Benign according to our data. Variant chr16-56519904-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261978.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS2	NM_031885.5 link	c.-42T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17	ENST00000245157.11	NP_114091.4
BBS2	NM_031885.5 link	c.-42T>G		5_prime_UTR_variant	Exon 1 of 17	ENST00000245157.11	NP_114091.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS2	ENST00000245157.11 link	c.-42T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 17	1	NM_031885.5	ENSP00000245157.5
BBS2	ENST00000245157.11 link	c.-42T>G		5_prime_UTR_variant	Exon 1 of 17	1	NM_031885.5	ENSP00000245157.5

Frequencies

GnomAD3 genomes

AF:

0.0774

AC:

11783

AN:

152156

Hom.:

667

Cov.:

show subpopulations

Gnomad AFR

AF:

0.144

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.0495

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:

0.0683

AC:

16622

AN:

243496

AF XY:

0.0695

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:

0.0436

Gnomad NFE exome

AF:

0.0396

Gnomad OTH exome

AF:

0.0588

GnomAD4 exome

AF:

0.0508

AC:

70738

AN:

1393800

Hom.:

2694

Cov.:

AF XY:

0.0526

AC XY:

36627

AN XY:

696708

show subpopulations

African (AFR)

AF:

0.147

AC:

4695

AN:

31946

American (AMR)

AF:

0.0498

AC:

2207

AN:

44346

Ashkenazi Jewish (ASJ)

AF:

0.0198

AC:

508

AN:

25652

East Asian (EAS)

AF:

0.121

AC:

4731

AN:

39226

South Asian (SAS)

AF:

0.126

AC:

10632

AN:

84544

European-Finnish (FIN)

AF:

0.0440

AC:

2326

AN:

52870

Middle Eastern (MID)

AF:

0.0467

AC:

263

AN:

5636

European-Non Finnish (NFE)

AF:

0.0398

AC:

41829

AN:

1051556

Other (OTH)

AF:

0.0611

AC:

3547

AN:

58024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

3020

6039

9059

12078

15098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1702

3404

5106

6808

8510

<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:

11808

AN:

152274

Hom.:

672

Cov.:

AF XY:

0.0791

AC XY:

5886

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.144

AC:

5999

AN:

41550

American (AMR)

AF:

0.0494

AC:

756

AN:

15306

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:

4822

European-Finnish (FIN)

AF:

0.0507

AC:

538

AN:

10616

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0418

AC:

2840

AN:

68018

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

549

1098

1646

2195

2744

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

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

May 10, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Bardet-Biedl syndrome 2

Benign:2

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Retinitis pigmentosa 74

Benign:1

Jun 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.49

PhyloP100

-2.4

PromoterAI

-0.014

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over