VCV000696445.17 - ClinVar

NM_001122955.4(BSCL2):c.1207GAG[1] (p.Glu404del)

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.

(7)

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.

Conflicting classifications of pathogenicity
Uncertain significance(4); Uncertain risk allele(1); Likely benign(2)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001122955.4(BSCL2):c.1207GAG[1] (p.Glu404del)

Variation ID: 696445 Accession: VCV000696445.17

Type and length

Microsatellite, 3 bp

Location

Cytogenetic: 11q12.3 11: 62690634-62690636 (GRCh38) [ NCBI UCSC ] 11: 62458106-62458108 (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	Dec 17, 2019	Nov 24, 2024	Jan 22, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001122955.4:c.1207GAG[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001116427.1:p.Glu404del	inframe deletion
NM_001122955.3:c.1210_1212del
NM_001130702.2:c.*9GAG[1]		3 prime UTR
NM_001386027.1:c.1213GAG[1]	NP_001372956.1:p.Glu406del	inframe deletion
NM_001386028.1:c.1207GAG[1]	NP_001372957.1:p.Glu404del	inframe deletion
NM_032667.6:c.1015GAG[1]	NP_116056.3:p.Glu340del	inframe deletion
NM_032667.6:c.1018_1020del
NM_032667.6:c.1018_1020delGAG		inframe deletion
NR_037946.1:n.3727GAG[1]		non-coding transcript variant
NC_000011.10:g.62690634CTC[1]
NC_000011.9:g.62458106CTC[1]
NG_008461.1:g.23936GAG[1]
NG_033077.1:g.4261GAG[1]
LRG_235:g.23936GAG[1]
LRG_235t2:c.1015GAG[1]	LRG_235p2:p.Glu340del

... more HGVS ... less HGVS

Protein change

E340del, E404del, E406del

Other names

p.Glu340del

Canonical SPDI

NC_000011.10:62690633:CTCCTC:CTC

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.

0.00140 (CTC)

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

Links

dbSNP: rs556562410 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.
BSCL2		-	-	GRCh38 GRCh37	8	578
HNRNPUL2-BSCL2	-	-	-	GRCh38	-	608

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.
Charcot-Marie-Tooth disease type 2	Likely benign (1)	criteria provided, single submitter	Jan 22, 2024	RCV000862805.9
Monogenic diabetes	Uncertain significance (1)	criteria provided, single submitter	Jan 5, 2018	RCV001174399.2
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	Nov 3, 2021	RCV002345950.2
Congenital generalized lipodystrophy type 2	Uncertain significance/Uncertain risk allele (2)	criteria provided, multiple submitters, no conflicts	Feb 10, 2022	RCV002468078.2
not provided	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Dec 11, 2023	RCV003442125.2

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.
Uncertain significance (Jan 05, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Monogenic diabetes Affected status: unknown Allele origin: unknown	Personalized Diabetes Medicine Program, University of Maryland School of Medicine Accession: SCV001337537.1 First in ClinVar: Jun 14, 2020 Last updated: Jun 14, 2020	Comment: ACMG criteria: PM4 (nonframeshift)=VUS Number of individuals with the variant: 1 Zygosity: Single Heterozygote
Uncertain significance (Feb 10, 2022)	criteria provided, single submitter (NYGC Assertion Criteria 2020) Method: clinical testing	Congenital generalized lipodystrophy type 2 Affected status: unknown Allele origin: germline	New York Genome Center Accession: SCV002764375.1 First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022	Observation 1: Clinical Features: Insulin resistance (present) , Diabetes mellitus (present) , Crohn disease (present) Zygosity: Single Heterozygote Secondary finding: no Observation 2: Clinical Features: Type 2 diabetes mellitus (present) , Hepatic steatosis (present) Zygosity: Single Heterozygote Secondary finding: no
Uncertain significance (Oct 13, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV004167963.1 First in ClinVar: Nov 25, 2023 Last updated: Nov 25, 2023	Comment: In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports that this variant does not alter protein structure/function; Has not been … (more) In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge (less)
Likely benign (Jan 22, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Charcot-Marie-Tooth disease type 2 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001003359.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Uncertain risk allele (-)	criteria provided, single submitter (K And H Uppaluri Personalized Medicine Clinic Variant Classification And Assertion Criteria Updated V 2) Method: research	Congenital generalized lipodystrophy type 2 (Autosomal recessive inheritance) Affected status: unknown Allele origin: unknown	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic Accession: SCV004698138.1 First in ClinVar: Mar 10, 2024 Last updated: Mar 10, 2024	Publications: PubMed (3) PubMed: 35351089‚ 18690553‚ 31824185 Comment: Potent mutations in BSCL2 gene are associated with Congenital generalized lipodystrophy, type 2, which can present with insulin resistance, fatty liver and diabetes.However, the role … (more) Potent mutations in BSCL2 gene are associated with Congenital generalized lipodystrophy, type 2, which can present with insulin resistance, fatty liver and diabetes.However, the role of this particular variant rs556562410 of Congenital Generalized Lipodystrophy type 2 remains uncertain (less)
Likely benign (Nov 03, 2021)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002653293.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more) This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Uncertain significance (Dec 11, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV005412348.1 First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024	Comment: BS1, PM4 Number of individuals with the variant: 1

Comment:

Potent mutations in BSCL2 gene are associated with Congenital generalized lipodystrophy, type 2, which can present with insulin resistance, fatty liver and diabetes.However, the role of this particular variant rs556562410 of Congenital Generalized Lipodystrophy type 2 remains uncertain

Comment:

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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
The neonatal onset diabetes mellitus of Chinese neonate with congenital generalized lipodystrophy 2: a case report.	Yang Y	BMC endocrine disorders	2022	PMID: 35351089
A New Compound Heterozygous Mutation Of BSCL2 In A Chinese Zhuang Ethnic Family With Congenital Generalized Lipodystrophy.	Qin YY	Diabetes, metabolic syndrome and obesity : targets and therapy	2019	PMID: 31824185
Congenital generalized lipodystrophy in an Indian patient with a novel mutation in BSCL2 gene.	Shirwalkar HU	Journal of inherited metabolic disease	2008	PMID: 18690553

Text-mined citations for rs556562410 ...

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 30, 2024

ClinVar Genomic variation as it relates to human health

NM_001122955.4(BSCL2):c.1207GAG[1] (p.Glu404del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs556562410 ...