NM_024685.4(BBS10):c.1736A>G (p.Lys579Arg) AND Bardet-Biedl syndrome 10

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Oct 27, 2021
Review status:: criteria provided, conflicting classifications

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:: RCV000675134.13

Allele description [Variation Report for NM_024685.4(BBS10):c.1736A>G (p.Lys579Arg)]

NM_024685.4(BBS10):c.1736A>G (p.Lys579Arg)

Gene:

BBS10:Bardet-Biedl syndrome 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q21.2

Genomic location:

Preferred name:

NM_024685.4(BBS10):c.1736A>G (p.Lys579Arg)

HGVS:

NC_000012.12:g.76346249T>C
NG_016357.1:g.7194A>G
NM_024685.4:c.1736A>GMANE SELECT
NP_078961.3:p.Lys579Arg
LRG_1255t1:c.1736A>G
LRG_1255:g.7194A>G
LRG_1255p1:p.Lys579Arg
NC_000012.11:g.76740029T>C
NM_024685.3:c.1736A>G
Q8TAM1:p.Lys579Arg

Protein change:

K579R

Links:

UniProtKB: Q8TAM1#VAR_026404; dbSNP: rs141521925

NCBI 1000 Genomes Browser:

rs141521925

Molecular consequence:

NM_024685.4:c.1736A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Bardet-Biedl syndrome 10 (BBS10)
Identifiers:: MONDO: MONDO:0014438; MedGen: C1859568; Orphanet: 110; OMIM: 615987

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001269804	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Jan 13, 2018)	germline	clinical testing	Citation Link,
SCV002060330	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))	Uncertain significance (Oct 27, 2021)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16582908, 24488770, 20498079 Citation Link,
SCV002091745	Natera, Inc.	no assertion criteria provided	Uncertain significance (Feb 13, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001269804

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Likely benign
(Jan 13, 2018)

germline

clinical testing

Citation Link,

SCV002060330

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Women's Health Autosomal Recessive and X-Linked Classification Criteria (2021))

Uncertain significance
(Oct 27, 2021)

unknown

clinical testing

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

Citation Link,

SCV002091745

Natera, Inc.

no assertion criteria provided

Uncertain significance
(Feb 13, 2020)

germline

clinical testing

Help

Summary from all submissions

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

Citations

PubMed

BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus.

Stoetzel C, Laurier V, Davis EE, Muller J, Rix S, Badano JL, Leitch CC, Salem N, Chouery E, Corbani S, Jalk N, Vicaire S, Sarda P, Hamel C, Lacombe D, Holder M, Odent S, Holder S, Brooks AS, Elcioglu NH, Silva ED, Rossillion B, et al.

Nat Genet. 2006 May;38(5):521-4. Epub 2006 Apr 2. Erratum in: Nat Genet. 2006 Jun;38(6):727. Da Silva, Eduardo [corrected to Silva, Eduardo D].

PubMed [citation]

PMID:: 16582908

IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome.

Aldahmesh MA, Li Y, Alhashem A, Anazi S, Alkuraya H, Hashem M, Awaji AA, Sogaty S, Alkharashi A, Alzahrani S, Al Hazzaa SA, Xiong Y, Kong S, Sun Z, Alkuraya FS.

Hum Mol Genet. 2014 Jun 15;23(12):3307-15. doi: 10.1093/hmg/ddu044. Epub 2014 Jan 31.

PubMed [citation]

PMID:: 24488770
PMCID:: PMC4047285

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001269804.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

#	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 Myriad Genetics, Inc., SCV002060330.2

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

Description

NM_024685.3(BBS10):c.1736A>G(K579R) is a missense variant classified as a variant of uncertain significance in the context of Bardet-Biedl syndrome. K579R has been observed in cases with relevant disease (PMID: 16582908, 24488770). Functional assessments of this variant are available in the literature (PMID: 20498079). K579R has been observed in population frequency databases (gnomAD: AFR 0.46%). In summary, there is insufficient evidence to classify NM_024685.3(BBS10):c.1736A>G(K579R) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.

#	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 Natera, Inc., SCV002091745.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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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