VCV000843618.10 - ClinVar

NM_031885.5(BBS2):c.1624G>T (p.Gly542Cys)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (3)

3 out of 5 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_031885.5(BBS2):c.1624G>T (p.Gly542Cys)

Variation ID: 843618 Accession: VCV000843618.10

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16q13 16: 56498472 (GRCh38) [ NCBI UCSC ] 16: 56532384 (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 15, 2020	Jul 13, 2025	May 29, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_031885.5:c.1624G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_114091.4:p.Gly542Cys	missense
NM_001377456.1:c.1624G>T	NP_001364385.1:p.Gly542Cys	missense
NR_165293.1:n.1914G>T		non-coding transcript variant
NR_165294.1:n.1911G>T		non-coding transcript variant
NR_165295.1:n.1742G>T		non-coding transcript variant
NR_165296.1:n.1614G>T		non-coding transcript variant
NR_165297.1:n.1614G>T		non-coding transcript variant
NC_000016.10:g.56498472C>A
NC_000016.9:g.56532384C>A
NG_009312.2:g.26553G>T

... more HGVS ... less HGVS

Protein change

G542C

Other names

Canonical SPDI

NC_000016.10:56498471:C:A

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.

0.00020 (T)

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

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Links

ClinGen: CA395976530 dbSNP: rs556899786 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	1327	1397

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	Uncertain significance (1)	criteria provided, single submitter	Aug 16, 2022	RCV001046291.5
Bardet-Biedl syndrome 2	Uncertain significance (1)	no assertion criteria provided	Feb 6, 2020	RCV001827288.1
Bardet-Biedl syndrome 2 Retinitis pigmentosa 74	Uncertain significance (1)	criteria provided, single submitter	Jun 18, 2024	RCV002481924.2
BBS2-related disorder	Uncertain significance (1)	no assertion criteria provided	Mar 23, 2024	RCV004733121.1
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	May 29, 2025	RCV005520393.1

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.	Expand all rows Collapse all rows 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.
Uncertain significance (Aug 16, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Bardet-Biedl syndrome	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001210188.4 First in ClinVar: Apr 15, 2020 Last updated: Feb 07, 2023	Comment: show This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 542 of the BBS2 protein (p.Gly542Cys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BBS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 843618). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Jun 18, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Bardet-Biedl syndrome 2 Retinitis pigmentosa 74 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Fulgent Genetics, Fulgent Genetics Accession: SCV002793813.2 First in ClinVar: Dec 31, 2022 Last updated: Jan 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (May 29, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV006201015.1 First in ClinVar: Jul 13, 2025 Last updated: Jul 13, 2025	Comment: show The c.1624G>T (p.G542C) alteration is located in exon 13 (coding exon 13) of the BBS2 gene. This alteration results from a G to T substitution at nucleotide position 1624, causing the glycine (G) at amino acid position 542 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Feb 06, 2020) N Not contributing to aggregate classification	no assertion criteria provided	Bardet-Biedl syndrome type 2	Natera, Inc. Accession: SCV002089267.1 First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Mar 23, 2024) N Not contributing to aggregate classification	no assertion criteria provided	BBS2-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV005343337.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: show The BBS2 c.1624G>T variant is predicted to result in the amino acid substitution p.Gly542Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 542 of the BBS2 protein (p.Gly542Cys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BBS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 843618). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

The c.1624G>T (p.G542C) alteration is located in exon 13 (coding exon 13) of the BBS2 gene. This alteration results from a G to T substitution at nucleotide position 1624, causing the glycine (G) at amino acid position 542 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Comment:

The BBS2 c.1624G>T variant is predicted to result in the amino acid substitution p.Gly542Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs556899786 ...

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 Apr 13, 2026