rs141170836

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000245157.11(BBS2):c.*13C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,609,052 control chromosomes in the GnomAD database, including 169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 17 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 152 hom. )

Consequence

BBS2
ENST00000245157.11 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.00

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 (BayesDel_noAF=-0.89).

BP6

Variant 16-56484748-G-A is Benign according to our data. Variant chr16-56484748-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 261976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0682 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.*13C>T		3_prime_UTR_variant	17/17	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.*13C>T		3_prime_UTR_variant	17/17	1	NM_031885.5	ENSP00000245157	P1

Frequencies

GnomAD3 genomes

AF:

0.00633

AC:

963

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0426

Gnomad ASJ

AF:

0.000867

Gnomad EAS

AF:

0.0210

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0128

AC:

3223

AN:

250980

Hom.:

AF XY:

0.0100

AC XY:

1360

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.0735

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.0203

Gnomad SAS exome

AF:

0.000688

Gnomad FIN exome

AF:

0.00865

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00914

GnomAD4 exome

AF:

0.00362

AC:

5269

AN:

1456782

Hom.:

152

Cov.:

AF XY:

0.00327

AC XY:

2373

AN XY:

725032

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.0702

Gnomad4 ASJ exome

AF:

0.000499

Gnomad4 EAS exome

AF:

0.0279

Gnomad4 SAS exome

AF:

0.000569

Gnomad4 FIN exome

AF:

0.00887

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.00435

GnomAD4 genome

AF:

0.00632

AC:

962

AN:

152270

Hom.:

Cov.:

AF XY:

0.00731

AC XY:

544

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.0425

Gnomad4 ASJ

AF:

0.000867

Gnomad4 EAS

AF:

0.0210

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.00883

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 13, 2017	Variant summary: The BBS2 c.*13C>T variant involves the alteration of a non-conserved nucleotide located in 3-prime untranslated region of exon 17. Mutation taster predicts a benign outcome for this variant. This variant was found in 1175/118352 control chromosomes (including 35 homozygotes), predominantly observed in the Latino subpopulation at a frequency of 0.077996 (872/11180). This frequency is about 92 times the estimated maximal expected allele frequency of a pathogenic BBS2 variant (0.0008452), suggesting this is a benign polymorphism found primarily in the populations of Latino origin. In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign/benign. Taken together, this variant is classified as Benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 23, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Bardet-Biedl syndrome 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.029

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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