NM_152618.3(BBS12):c.424dup (p.Asp142fs) AND Bardet-Biedl syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 4, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001246835.5

Allele description [Variation Report for NM_152618.3(BBS12):c.424dup (p.Asp142fs)]

NM_152618.3(BBS12):c.424dup (p.Asp142fs)

Gene:

BBS12:Bardet-Biedl syndrome 12 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

4q27

Genomic location:

Preferred name:

NM_152618.3(BBS12):c.424dup (p.Asp142fs)

HGVS:

NC_000004.12:g.122742316dup
NG_021203.1:g.14615dup
NM_001178007.2:c.424dup
NM_152618.3:c.424dupMANE SELECT
NP_001171478.1:p.Asp142fs
NP_689831.2:p.Asp142fs
NC_000004.11:g.123663469_123663470insG
NC_000004.11:g.123663471dup
NM_152618.2:c.424dup
NM_152618.2:c.424dupG

Protein change:

D142fs

Links:

dbSNP: rs1553941258

NCBI 1000 Genomes Browser:

rs1553941258

Molecular consequence:

NM_001178007.2:c.424dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_152618.3:c.424dup - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001420222	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 4, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20827784, 21642631, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001420222

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 4, 2023)

germline

clinical testing

PubMed (3)
[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

Two sibs with Bardet-Biedl syndrome due to mutations in BBS12: no clues for modulation by a third mutation in BBS10.

Dulfer E, Hoefsloot LH, Timmer A, Mom C, van Essen AJ.

Am J Med Genet A. 2010 Oct;152A(10):2666-9. doi: 10.1002/ajmg.a.33650. No abstract available.

PubMed [citation]

PMID:: 20827784

Molecular analysis of Bardet-Biedl syndrome families: report of 21 novel mutations in 10 genes.

Chen J, Smaoui N, Hammer MB, Jiao X, Riazuddin SA, Harper S, Katsanis N, Riazuddin S, Chaabouni H, Berson EL, Hejtmancik JF.

Invest Ophthalmol Vis Sci. 2011 Jul 18;52(8):5317-24. doi: 10.1167/iovs.11-7554.

PubMed [citation]

PMID:: 21642631
PMCID:: PMC3176075

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001420222.4

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BBS12 protein in which other variant(s) (p.Arg675*) have been determined to be pathogenic (PMID: 20827784, 21642631). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 555890). This variant has not been reported in the literature in individuals affected with BBS12-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp142Glyfs*10) in the BBS12 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 569 amino acid(s) of the BBS12 protein.

#	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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