NM_024685.4(BBS10):c.2122_2123del (p.Lys708fs) AND Bardet-Biedl syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 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:: RCV001328243.3

Allele description [Variation Report for NM_024685.4(BBS10):c.2122_2123del (p.Lys708fs)]

NM_024685.4(BBS10):c.2122_2123del (p.Lys708fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

12q21.2

Genomic location:

Preferred name:

NM_024685.4(BBS10):c.2122_2123del (p.Lys708fs)

HGVS:

NC_000012.12:g.76345862_76345863del
NG_016357.1:g.7580_7581del
NM_024685.4:c.2122_2123delMANE SELECT
NP_078961.3:p.Lys708fs
LRG_1255t1:c.2122_2123del
LRG_1255:g.7580_7581del
LRG_1255p1:p.Lys708fs
NC_000012.11:g.76739642_76739643del
NM_024685.3:c.2122_2123del

Protein change:

K708fs

Links:

dbSNP: rs1951753208

NCBI 1000 Genomes Browser:

rs1951753208

Molecular consequence:

NM_024685.4:c.2122_2123del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Bardet-Biedl syndrome (BBS)
Identifiers:: MONDO: MONDO:0015229; MedGen: C0752166; Orphanet: 110; OMIM: PS209900

Recent activity

Clear Turn Off Turn On

Croton antanosiensis voucher MICH:Van Ee et al. 958 tRNA-Lys (trnK) gene, intron...
Croton antanosiensis voucher MICH:Van Ee et al. 958 tRNA-Lys (trnK) gene, intron; and maturase K (matK) gene, complete cds; chloroplast
gi|1240516518|gb|KY039670.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001449191	Sydney Genome Diagnostics, Children's Hospital Westmead	no assertion criteria provided	Likely pathogenic (Aug 22, 2018)	unknown	clinical testing
SCV004628537	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 4, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29666954, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001449191

Sydney Genome Diagnostics, Children's Hospital Westmead

no assertion criteria provided

Likely pathogenic
(Aug 22, 2018)

unknown

clinical testing

SCV004628537

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 4, 2023)

germline

clinical testing

PubMed (2)
[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	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical characteristics of a Japanese patient with Bardet-Biedl syndrome caused by BBS10 mutations.

Kurata K, Hosono K, Hikoya A, Kato A, Saitsu H, Minoshima S, Ogata T, Hotta Y.

Jpn J Ophthalmol. 2018 Jul;62(4):458-466. doi: 10.1007/s10384-018-0591-8. Epub 2018 Apr 17.

PubMed [citation]

PMID:: 29666954

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Sydney Genome Diagnostics, Children's Hospital Westmead, SCV001449191.1

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

Description

This individual is heterozygous for the c.2122_2123del variant in the BBS10 gene. The variant has not been reported in any population databases (i.e. gnomAD, ExAC, ESP or dbSNP). To our knowledge, this variant has not been previously reported in the literature or any disease specific databases. This frameshifting variant p.(Lys708Glufs*14) is predicted to affect only the last 16 amino acids of the BBS10 protein. However, other truncating variants in this region have been described in ClinVar as pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/?term=bbs10[gene]). This variant is considered to be likely pathogenic according to the ACMG guidelines.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004628537.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Lys708Glufs*14) in the BBS10 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 16 amino acid(s) of the BBS10 protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BBS10 protein in which other variant(s) (p.Arg709*) have been determined to be pathogenic (PMID: 29666954). 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: 988217). This variant has not been reported in the literature in individuals affected with BBS10-related conditions. This variant is not present in population databases (gnomAD no frequency).

#	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

ClinVar

Relating variation to medicine