NM_024649.5(BBS1):c.1285C>T (p.Arg429Ter) AND Bardet-Biedl syndrome

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Oct 29, 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:: RCV000169362.22

Allele description [Variation Report for NM_024649.5(BBS1):c.1285C>T (p.Arg429Ter)]

NM_024649.5(BBS1):c.1285C>T (p.Arg429Ter)

Genes:

BBS1:Bardet-Biedl syndrome 1 [Gene - OMIM - HGNC]
ZDHHC24:zDHHC palmitoyltransferase 24 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_024649.5(BBS1):c.1285C>T (p.Arg429Ter)

HGVS:

NC_000011.10:g.66526753C>T
NG_009093.1:g.21106C>T
NM_001348571.2:c.*21+183G>A
NM_024649.5:c.1285C>TMANE SELECT
NP_078925.3:p.Arg429Ter
NC_000011.9:g.66294224C>T
NM_024649.4:c.1285C>T

Protein change:

R429*

Links:

dbSNP: rs768443448

NCBI 1000 Genomes Browser:

rs768443448

Molecular consequence:

NM_001348571.2:c.*21+183G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_024649.5:c.1285C>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000220733	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Sep 24, 2014)	unknown	literature only	PubMed (5) [See all records that cite these PMIDs] 20876674, 15770229, 20177705, 21517826, 12677556 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV000699513	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (May 10, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12677556, 15770229, 20177705, 21517826, 20876674, 32451492, 32165824 Citation Link,
SCV000826045	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 29, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12118255, 21520335, 27032803, 12677556, 15770229, 20876674, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000220733

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(Sep 24, 2014)

unknown

literature only

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

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV000699513

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(May 10, 2021)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link,

SCV000826045

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 29, 2023)

germline

clinical testing

PubMed (7)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Identification of 28 novel mutations in the Bardet-Biedl syndrome genes: the burden of private mutations in an extensively heterogeneous disease.

Muller J, Stoetzel C, Vincent MC, Leitch CC, Laurier V, Danse JM, Hellé S, Marion V, Bennouna-Greene V, Vicaire S, Megarbane A, Kaplan J, Drouin-Garraud V, Hamdani M, Sigaudy S, Francannet C, Roume J, Bitoun P, Goldenberg A, Philip N, Odent S, Green J, et al.

Hum Genet. 2010 Mar;127(5):583-93. doi: 10.1007/s00439-010-0804-9. Epub 2010 Feb 23.

PubMed [citation]

PMID:: 20177705
PMCID:: PMC3638942

Hippocampal dysgenesis and variable neuropsychiatric phenotypes in patients with Bardet-Biedl syndrome underline complex CNS impact of primary cilia.

Bennouna-Greene V, Kremer S, Stoetzel C, Christmann D, Schuster C, Durand M, Verloes A, Sigaudy S, Holder-Espinasse M, Godet J, Brandt C, Marion V, Danion A, Dietemann JL, Dollfus H.

Clin Genet. 2011 Dec;80(6):523-31. doi: 10.1111/j.1399-0004.2011.01688.x. Epub 2011 May 25.

PubMed [citation]

PMID:: 21517826

See all PubMed Citations (11)

Details of each submission

From Counsyl, SCV000220733.2

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

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699513.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

Variant summary: BBS1 c.1285C>T (p.Arg429X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 251846 control chromosomes. c.1285C>T has been reported in the literature in individuals affected with Bardet-Biedl Syndrome and in at-least one individual among a cohort of patients with Leber congenital amaurosis (example, Beales_2003, Hichri_2005, Surl_2020, Hirano_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=3)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was 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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000826045.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Arg429*) in the BBS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS1 are known to be pathogenic (PMID: 12118255, 21520335, 27032803). This variant is present in population databases (rs768443448, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 12677556, 15770229, 20876674). ClinVar contains an entry for this variant (Variation ID: 188983). 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: Apr 13, 2025

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