VCV000035755.10 - ClinVar

NM_031885.5(BBS2):c.1770del (p.Phe590fs)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(5)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_031885.5(BBS2):c.1770del (p.Phe590fs)

Variation ID: 35755 Accession: VCV000035755.10

Type and length

Deletion, 1 bp

Location

Cytogenetic: 16q13 16: 56497770 (GRCh38) [ NCBI UCSC ] 16: 56531682 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Jun 17, 2024	Mar 7, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_031885.5:c.1770del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_114091.4:p.Phe590fs	frameshift
NM_001377456.1:c.1770del	NP_001364385.1:p.Phe590fs	frameshift
NM_031885.3:c.1770del
NR_165293.1:n.2060del		non-coding transcript variant
NR_165294.1:n.2057del		non-coding transcript variant
NR_165295.1:n.1888del		non-coding transcript variant
NR_165296.1:n.1760del		non-coding transcript variant
NR_165297.1:n.1760del		non-coding transcript variant
NC_000016.10:g.56497773del
NC_000016.9:g.56531685del
NG_009312.2:g.27255del

... more HGVS ... less HGVS

Protein change

F590fs

Other names

Canonical SPDI

NC_000016.10:56497769:AAAA:AAA

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA260184 dbSNP: rs193922711 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
BBS2		-	-	GRCh38 GRCh37	1142	1180

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Bardet-Biedl syndrome 2	Pathogenic (2)	criteria provided, single submitter	Mar 7, 2024	RCV000190358.3
Bardet-Biedl syndrome	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	May 26, 2023	RCV000029407.8
BBS2-related disorder	Pathogenic (1)	criteria provided, single submitter	Jun 16, 2023	RCV004532405.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
likely pathogenic (Aug 18, 2011)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: curation, clinical testing	Bardet-Biedl Syndrome (autosomal unknown) Affected status: unknown, yes Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000052055.2 First in ClinVar: Apr 04, 2013 Last updated: Mar 28, 2022	Comment: Converted during submission to Likely pathogenic. Observation 1: Tissue: Blood Observation 2: Tissue: Blood
Pathogenic (Jun 16, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	BBS2-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004113179.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023	Comment: The BBS2 c.1770delT variant is predicted to result in a frameshift and premature protein termination (p.Phe590Leufs8). To our knowledge, this variant has not been reported … (more) The BBS2 c.1770delT variant is predicted to result in a frameshift and premature protein termination (p.Phe590Leufs8). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-56531681-CA-C). Frameshift variants in BBS2 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
Pathogenic (May 26, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Bardet-Biedl syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001230723.5 First in ClinVar: Apr 15, 2020 Last updated: Feb 20, 2024	Publications: PubMed (4) PubMed: 11285252‚ 20177705‚ 24608809‚ 26518167 Comment: For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 35755). This variant has not been … (more) For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 35755). This variant has not been reported in the literature in individuals affected with BBS2-related conditions. This variant is present in population databases (rs193922711, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Phe590Leufs*8) in the BBS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS2 are known to be pathogenic (PMID: 11285252, 20177705, 24608809, 26518167). (less)
Pathogenic (Mar 07, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Bardet-Biedl syndrome 2 Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004214016.2 First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024
Pathogenic (May 25, 2014)	no assertion criteria provided Method: clinical testing	Bardet-Biedl syndrome 2 Affected status: yes Allele origin: uniparental	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000153774.1 First in ClinVar: Aug 15, 2015 Last updated: Aug 15, 2015 Comment: 24-day-old female baby with whole chromosome UPD16 suspected to have Bardet-Biedl syndrome 2.	Comment: A homozygous frameshift mutation in exon 14 of BBS2 gene. Number of individuals with the variant: 1 Sex: female

Comment:

The BBS2 c.1770delT variant is predicted to result in a frameshift and premature protein termination (p.Phe590Leufs*8). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-56531681-CA-C). Frameshift variants in BBS2 are expected to be pathogenic. This variant is interpreted as pathogenic.

Comment:

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 35755). This variant has not been reported in the literature in individuals affected with BBS2-related conditions. This variant is present in population databases (rs193922711, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Phe590Leufs*8) in the BBS2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS2 are known to be pathogenic (PMID: 11285252, 20177705, 24608809, 26518167).

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Targeted multi-gene panel testing for the diagnosis of Bardet Biedl syndrome: Identification of nine novel mutations across BBS1, BBS2, BBS4, BBS7, BBS9, BBS10 genes.	Ece Solmaz A	European journal of medical genetics	2015	PMID: 26518167
Comprehensive molecular diagnosis of Bardet-Biedl syndrome by high-throughput targeted exome sequencing.	Xing DJ	PloS one	2014	PMID: 24608809
Identification of 28 novel mutations in the Bardet-Biedl syndrome genes: the burden of private mutations in an extensively heterogeneous disease.	Muller J	Human genetics	2010	PMID: 20177705
Positional cloning of a novel gene on chromosome 16q causing Bardet-Biedl syndrome (BBS2).	Nishimura DY	Human molecular genetics	2001	PMID: 11285252

Text-mined citations for rs193922711 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 19, 2024

ClinVar Genomic variation as it relates to human health

NM_031885.5(BBS2):c.1770del (p.Phe590fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs193922711 ...