NM_031885.5(BBS2):c.1206dup (p.Arg403fs) AND Bardet-Biedl syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Oct 14, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001192942.4

Allele description [Variation Report for NM_031885.5(BBS2):c.1206dup (p.Arg403fs)]

NM_031885.5(BBS2):c.1206dup (p.Arg403fs)

Gene:

BBS2:Bardet-Biedl syndrome 2 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

16q13

Genomic location:

Preferred name:

NM_031885.5(BBS2):c.1206dup (p.Arg403fs)

HGVS:

NC_000016.10:g.56501372dup
NG_009312.2:g.23653dup
NM_001377456.1:c.1206dup
NM_031885.5:c.1206dupMANE SELECT
NP_001364385.1:p.Arg403fs
NP_114091.4:p.Arg403fs
NC_000016.9:g.56535283_56535284insT
NC_000016.9:g.56535284dup
NG_009312.1:g.23912dup
NM_031885.3:c.1206dup
NR_165293.1:n.1368dup
NR_165294.1:n.1368dup
NR_165295.1:n.1368dup
NR_165296.1:n.1368dup
NR_165297.1:n.1368dup

Protein change:

R403fs

Links:

dbSNP: rs1964267396

NCBI 1000 Genomes Browser:

rs1964267396

Molecular consequence:

NM_001377456.1:c.1206dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_031885.5:c.1206dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_165293.1:n.1368dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165294.1:n.1368dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165295.1:n.1368dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165296.1:n.1368dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165297.1:n.1368dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Bardet-Biedl syndrome (BBS)
Identifiers:: MONDO: MONDO:0015229; MedGen: C0752166; Orphanet: 110; OMIM: PS209900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001361416	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Jun 14, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11285252, 21463199, 25541840, 11886943 Citation Link,
SCV003443555	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 14, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20177705, 24608809, 26518167, 11285252, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001361416

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Jun 14, 2019)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV003443555

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 14, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

BBS mutational analysis: a strategic approach.

Billingsley G, Deveault C, Héon E.

Ophthalmic Genet. 2011 Sep;32(3):181-7. doi: 10.3109/13816810.2011.567319. Epub 2011 Apr 4.

PubMed [citation]

PMID:: 21463199

Association between missense mutations in the BBS2 gene and nonsyndromic retinitis pigmentosa.

Shevach E, Ali M, Mizrahi-Meissonnier L, McKibbin M, El-Asrag M, Watson CM, Inglehearn CF, Ben-Yosef T, Blumenfeld A, Jalas C, Banin E, Sharon D.

JAMA Ophthalmol. 2015 Mar;133(3):312-8. doi: 10.1001/jamaophthalmol.2014.5251.

PubMed [citation]

PMID:: 25541840

See all PubMed Citations (8)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361416.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: BBS2 c.1206dupA (p.Arg403ThrfsX6) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251492 control chromosomes (gnomAD). c.1206dupA has been reported in the literature in a homozygous individual affected with Bardet-Biedl Syndrome (Nishimura_2001). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003443555.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Arg403Thrfs*6) in the BBS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS2 are known to be pathogenic (PMID: 11285252, 20177705, 24608809, 26518167). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with BBS2-related conditions (PMID: 11285252). This variant is also known as 1206insA. ClinVar contains an entry for this variant (Variation ID: 928684). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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