rs587777824

Variant names:

• chr16-56502672-CT-C
• rs587777824
• NM_031885.5:c.940delA

Variant summary

Our verdict is Pathogenic. The variant received 13 ACMG points: 13P and 0B. PVS1 PM2 PP3 PP5_Moderate

The NM_031885.5(BBS2):​c.940delA​(p.Ile314fs) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BBS2 NM_031885.5 frameshift, splice_region
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 2.16
• Publications: 2 publications found

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

ACMG classification

Our verdict: Pathogenic. The variant received 13 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant 16-56502672-CT-C is Pathogenic according to our data. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-56502672-CT-C is described in CliVar as Pathogenic. Clinvar id is 4568.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BBS2	NM_031885.5	c.940delA	p.Ile314fs	frameshift_variant, splice_region_variant	Exon 8 of 17	ENST00000245157.11	NP_114091.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BBS2	ENST00000245157.11	c.940delA	p.Ile314fs	frameshift_variant, splice_region_variant	Exon 8 of 17	1	NM_031885.5	ENSP00000245157.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Bardet-Biedl syndrome 2 Pathogenic:2

Apr 01, 2001

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Jun 05, 2023

Baylor Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.72		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.61		Position offset: 2
DS_DL_spliceai		0.72		Position offset: 1

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

Other links and lift over

dbSNP: rs587777824; hg19: chr16-56536584;