NM_024649.5(BBS1):c.1339G>A (p.Ala447Thr) AND Bardet-Biedl syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 31, 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:: RCV000638357.14

Allele description [Variation Report for NM_024649.5(BBS1):c.1339G>A (p.Ala447Thr)]

NM_024649.5(BBS1):c.1339G>A (p.Ala447Thr)

Genes:

BBS1:Bardet-Biedl syndrome 1 [Gene - OMIM - HGNC]
ZDHHC24:zinc finger DHHC-type containing 24 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.2

Genomic location:

Preferred name:

NM_024649.5(BBS1):c.1339G>A (p.Ala447Thr)

HGVS:

NC_000011.10:g.66526807G>A
NG_009093.1:g.21160G>A
NM_001348571.2:c.*21+129C>T
NM_024649.5:c.1339G>AMANE SELECT
NP_078925.3:p.Ala447Thr
NC_000011.9:g.66294278G>A
NM_024649.4:c.1339G>A

Protein change:

A447T

Links:

dbSNP: rs200116631

NCBI 1000 Genomes Browser:

rs200116631

Molecular consequence:

NM_001348571.2:c.*21+129C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_024649.5:c.1339G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Jupunba oppositifolia voucher Jack7251 external transcribed spacer and 18S ribos...
Jupunba oppositifolia voucher Jack7251 external transcribed spacer and 18S ribosomal RNA gene, partial sequence
gi|1824092757|gb|MN305241.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000759855	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 31, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 28341476, 32349990, 33594065, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000759855

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 31, 2023)

germline

clinical testing

PubMed (6)
[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

Panel-Based Clinical Genetic Testing in 85 Children with Inherited Retinal Disease.

Taylor RL, Parry NRA, Barton SJ, Campbell C, Delaney CM, Ellingford JM, Hall G, Hardcastle C, Morarji J, Nichol EJ, Williams LC, Douzgou S, Clayton-Smith J, Ramsden SC, Sharma V, Biswas S, Lloyd IC, Ashworth JL, Black GC, Sergouniotis PI.

Ophthalmology. 2017 Jul;124(7):985-991. doi: 10.1016/j.ophtha.2017.02.005. Epub 2017 Mar 22.

PubMed [citation]

PMID:: 28341476

Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence in an Inbred Population of Pakistan.

Saeed S, Arslan M, Manzoor J, Din SM, Janjua QM, Ayesha H, Ain QT, Inam L, Lobbens S, Vaillant E, Durand E, Derhourhi M, Amanzougarene S, Badreddine A, Berberian L, Gaget S, Khan WI, Butt TA, Bonnefond A, Froguel P.

Diabetes. 2020 Jul;69(7):1424-1438. doi: 10.2337/db19-1238. Epub 2020 Apr 29.

PubMed [citation]

PMID:: 32349990

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000759855.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 447 of the BBS1 protein (p.Ala447Thr). This variant also falls at the last nucleotide of exon 13, which is part of the consensus splice site for this exon. This variant is present in population databases (rs200116631, gnomAD 0.03%). This missense change has been observed in individual(s) with clinical features of Bardet-Biedl syndrome (PMID: 28341476, 32349990, 33594065; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 531824). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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: Nov 3, 2024

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