NM_031885.5(BBS2):c.72C>G (p.Tyr24Ter) AND Bardet-Biedl syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 20, 2024
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:: RCV000589350.9

Allele description [Variation Report for NM_031885.5(BBS2):c.72C>G (p.Tyr24Ter)]

NM_031885.5(BBS2):c.72C>G (p.Tyr24Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16q13

Genomic location:

Preferred name:

NM_031885.5(BBS2):c.72C>G (p.Tyr24Ter)

HGVS:

NC_000016.10:g.56519791G>C
NG_009312.2:g.5234C>G
NM_001377456.1:c.72C>G
NM_031885.5:c.72C>GMANE SELECT
NP_001364385.1:p.Tyr24Ter
NP_114091.3:p.Tyr24Ter
NP_114091.4:p.Tyr24Ter
NC_000016.9:g.56553703G>C
NG_009312.1:g.5493C>G
NM_031885.3:c.72C>G
NM_031885.4:c.72C>G
NR_165293.1:n.234C>G
NR_165294.1:n.234C>G
NR_165295.1:n.234C>G
NR_165296.1:n.234C>G
NR_165297.1:n.234C>G
c.72C>G (p.Tyr24*)

Protein change:

Y24*; TYR24TER

Links:

OMIM: 606151.0003; dbSNP: rs121908175

NCBI 1000 Genomes Browser:

rs121908175

Molecular consequence:

NR_165293.1:n.234C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165294.1:n.234C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165295.1:n.234C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165296.1:n.234C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_165297.1:n.234C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001377456.1:c.72C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_031885.5:c.72C>G - 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
SCV000699658	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Aug 10, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20177705, 20498079, 11567139 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV000940175	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 20, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 11285252, 20177705, 24608809, 26518167, 11567139, 21344540, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000699658

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Aug 10, 2017)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV000940175

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 20, 2024)

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

Citations

PubMed

Functional analyses of variants reveal a significant role for dominant negative and common alleles in oligogenic Bardet-Biedl syndrome.

Zaghloul NA, Liu Y, Gerdes JM, Gascue C, Oh EC, Leitch CC, Bromberg Y, Binkley J, Leibel RL, Sidow A, Badano JL, Katsanis N.

Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10602-7. doi: 10.1073/pnas.1000219107. Epub 2010 May 24.

PubMed [citation]

PMID:: 20498079
PMCID:: PMC2890780

Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2).

Nishimura DY, Searby CC, Carmi R, Elbedour K, Van Maldergem L, Fulton AB, Lam BL, Powell BR, Swiderski RE, Bugge KE, Haider NB, Kwitek-Black AE, Ying L, Duhl DM, Gorman SW, Heon E, Iannaccone A, Bonneau D, Biesecker LG, Jacobson SG, Stone EM, Sheffield VC.

Hum Mol Genet. 2001 Apr 1;10(8):865-74.

PubMed [citation]

PMID:: 11285252

See all PubMed Citations (8)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699658.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: The BBS2 c.72C>G (p.Tyr24X) variant results in a premature termination codon, predicted to cause a truncated or absent BBS2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 7/116822 control chromosomes at a frequency of 0.0000599, which does not exceed the estimated maximal expected allele frequency of a pathogenic BBS2 variant (0.0008452). This variant has been reported in multiple BBS patients in homozygous or compound heterozygous state. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is 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, SCV000940175.6

#	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.Tyr24*) 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 present in population databases (rs121908175, gnomAD 0.01%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 11567139, 21344540). ClinVar contains an entry for this variant (Variation ID: 4570). 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: Oct 13, 2024

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