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NM_031885.5(BBS2):c.1864C>T (p.Arg622Ter) AND Bardet-Biedl syndrome 2

Germline classification:
Pathogenic (4 submissions)
Last evaluated:
Sep 20, 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:
RCV000335732.8

Allele description [Variation Report for NM_031885.5(BBS2):c.1864C>T (p.Arg622Ter)]

NM_031885.5(BBS2):c.1864C>T (p.Arg622Ter)

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.1864C>T (p.Arg622Ter)
HGVS:
  • NC_000016.10:g.56497013G>A
  • NG_009312.2:g.28012C>T
  • NM_001377456.1:c.1864C>T
  • NM_031885.5:c.1864C>TMANE SELECT
  • NP_001364385.1:p.Arg622Ter
  • NP_114091.4:p.Arg622Ter
  • NC_000016.9:g.56530925G>A
  • NG_009312.1:g.28271C>T
  • NM_031885.3:c.1864C>T
  • NR_165293.1:n.2154C>T
  • NR_165294.1:n.2151C>T
  • NR_165295.1:n.1982C>T
  • NR_165296.1:n.1854C>T
  • NR_165297.1:n.1854C>T
Protein change:
R622*
Links:
dbSNP: rs201196733
NCBI 1000 Genomes Browser:
rs201196733
Molecular consequence:
  • NR_165293.1:n.2154C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_165294.1:n.2151C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_165295.1:n.1982C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_165296.1:n.1854C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_165297.1:n.1854C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001377456.1:c.1864C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_031885.5:c.1864C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Bardet-Biedl syndrome 2 (BBS2)
Identifiers:
MONDO: MONDO:0014432; MedGen: C2936863; Orphanet: 110; OMIM: 615981

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000486377Counsyl
no assertion criteria provided
Likely pathogenic
(Nov 2, 2016)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000916672Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Pathogenic
(Mar 2, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002557552Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Feb 2, 2022)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV004214002Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Sep 20, 2023)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

BBS genotype-phenotype assessment of a multiethnic patient cohort calls for a revision of the disease definition.

Deveault C, Billingsley G, Duncan JL, Bin J, Theal R, Vincent A, Fieggen KJ, Gerth C, Noordeh N, Traboulsi EI, Fishman GA, Chitayat D, Knueppel T, Millán JM, Munier FL, Kennedy D, Jacobson SG, Innes AM, Mitchell GA, Boycott K, Héon E.

Hum Mutat. 2011 Jun;32(6):610-9. doi: 10.1002/humu.21480. Epub 2011 Mar 22.

PubMed [citation]
PMID:
21344540

Whole Exome Sequencing Identifies a Novel and a Recurrent Mutation in BBS2 Gene in a Family with Bardet-Biedl Syndrome.

Bee YM, Chawla M, Zhao Y.

Biomed Res Int. 2015;2015:524754. doi: 10.1155/2015/524754. Epub 2015 May 11.

PubMed [citation]
PMID:
26078953
PMCID:
PMC4442282
See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000486377.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000916672.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Variant summary: BBS2 c.1864C>T (p.Arg622X) 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. A truncation downstream of this position has been classified as likely pathogenic by our laboratory, c.2107C>T (p.Arg703X). The variant has been observed with an allele frequency of 2.8e-05 in 246196 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BBS2 causing Bardet-Biedl Syndrome (2.8e-05 vs. 8.5e-04), allowing no conclusion about variant significance. The variant, c.1864C>T, has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (Bee 2015, Deveault 2011). 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. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) have classified the variant as "likely pathogenic/pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002557552.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Bardet-Biedl syndrome 2 (MIM#615981) and retinitis pigmentosa 74 (MIM#616562). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2: 7 heterozygotes, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (Decipher; PMID: 31283077). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been classified as likely pathogenic or pathogenic by clinical diagnostic laboratories and has been reported as compound heterozygous in individuals with Bardet-Biedl syndrome 2 (ClinVar; PMIDs: 21344540, 26078953). This variant is also compound heterozygous in one individual with chronic kidney disease without a specific diagnosis and heterozygous in an individual with inherited retinal disease (PMIDs: 33226606, 31429209). (SP) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV004214002.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 28, 2024