rs115078074

Variant names:

• chr16-56519902-A-G
• rs115078074
• NM_031885.5:c.-40T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0260

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]

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 261977.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-56519902-A-G is described in Lovd as [Benign].
• 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	c.-40T>C		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	c.-40T>C		5_prime_UTR_variant	Exon 1 of 17	1	NM_031885.5	ENSP00000245157.5

Frequencies

GnomAD3 genomes AF: 0.0774 AC: 11781 AN: 152142 Hom.: 666 Cov.: 32

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

GnomAD3 exomes AF: 0.0684 AC: 16694 AN: 244210 Hom.: 862 AF XY: 0.0696 AC XY: 9235 AN XY: 132728

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 SAS exome AF: 0.129

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.: 23 AF XY: 0.0526 AC XY: 36789 AN XY: 700044

Gnomad4 AFR exome AF: 0.147

Gnomad4 AMR exome AF: 0.0498

Gnomad4 ASJ exome AF: 0.0198

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0441

Gnomad4 NFE exome AF: 0.0398

Gnomad4 OTH exome AF: 0.0612

GnomAD4 genome AF: 0.0775 AC: 11806 AN: 152260 Hom.: 671 Cov.: 32 AF XY: 0.0791 AC XY: 5885 AN XY: 74446

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0494

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.0507

Gnomad4 NFE AF: 0.0417

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0554 Hom.: 54

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

Submissions by phenotype

Bardet-Biedl syndrome 2 Benign:2

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. -

Jun 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

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	-0.87
CADD	Benign	7.0
DANN	Benign	0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs115078074; hg19: chr16-56553814; COSMIC: COSV55325973; COSMIC: COSV55325973;