VCV002122286.2 - ClinVar

NM_001370658.1(BTD):c.1130_1155dup (p.Val386delinsArgTer)

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.

(1)

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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001370658.1(BTD):c.1130_1155dup (p.Val386delinsArgTer)

Variation ID: 2122286 Accession: VCV002122286.2

Type and length

Duplication, 26 bp

Location

Cytogenetic: 3p25.1 3: 15645042-15645043 (GRCh38) [ NCBI UCSC ] 3: 15686549-15686550 (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	Feb 8, 2023	Feb 20, 2024	Aug 1, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_001370658.1:c.1130_1155dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001357587.1:p.Val386delinsArgTer	nonsense
NM_000060.4:c.1190_1215dup	NP_000051.1:p.Val406Argfs	frameshift
NM_001281723.4:c.1130_1155dup	NP_001268652.2:p.Val386Argfs	frameshift
NM_001281724.3:c.1130_1155dup	NP_001268653.2:p.Val386delinsArgTer	nonsense
NM_001281725.3:c.1130_1155dup	NP_001268654.1:p.Val386Argfs	frameshift
NM_001323582.2:c.1130_1155dup	NP_001310511.1:p.Val386Argfs	frameshift
NM_001370752.1:c.1015+115_1015+140dup		intron variant
NM_001370753.1:c.399+2989_399+3014dup		intron variant
NM_001407364.1:c.1130_1155dup	NP_001394293.1:p.Val386Argfs	frameshift
NM_001407365.1:c.1130_1155dup	NP_001394294.1:p.Val386Argfs	frameshift
NM_001407366.1:c.1130_1155dup	NP_001394295.1:p.Val386Argfs	frameshift
NM_001407367.1:c.1130_1155dup	NP_001394296.1:p.Val386Argfs	frameshift
NM_001407368.1:c.1130_1155dup	NP_001394297.1:p.Val386Argfs	frameshift
NM_001407369.1:c.1130_1155dup	NP_001394298.1:p.Val386Argfs	frameshift
NM_001407370.1:c.1130_1155dup	NP_001394299.1:p.Val386Argfs	frameshift
NM_001407371.1:c.1130_1155dup	NP_001394300.1:p.Val386Argfs	frameshift
NM_001407372.1:c.1130_1155dup	NP_001394301.1:p.Val386Argfs	frameshift
NM_001407373.1:c.1130_1155dup	NP_001394302.1:p.Val386Argfs	frameshift
NM_001407374.1:c.1130_1155dup	NP_001394303.1:p.Val386Argfs	frameshift
NM_001407375.1:c.1130_1155dup	NP_001394304.1:p.Val386Argfs	frameshift
NM_001407376.1:c.1130_1155dup	NP_001394305.1:p.Val386Argfs	frameshift
NM_001407377.1:c.1130_1155dup	NP_001394306.1:p.Val386Argfs	frameshift
NM_001407378.1:c.1130_1155dup	NP_001394307.1:p.Val386Argfs	frameshift
NC_000003.12:g.15645046_15645071dup
NC_000003.11:g.15686553_15686578dup
NG_008019.2:g.48695_48720dup
NG_008019.3:g.48696_48721dup

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000003.12:15645042:CTGAGATGATGTATGACAATTTCACCCTG:CTGAGATGATGTATGACAATTTCACCCTGAGATGATGTATGACAATTTCACCCTG

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

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.
BTD		-	-	GRCh38 GRCh37	667	753

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.
Biotinidase deficiency	Pathogenic (1)	criteria provided, single submitter	Aug 1, 2022	RCV003053974.3

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.
Pathogenic (Aug 01, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Biotinidase deficiency Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003344174.2 First in ClinVar: Feb 07, 2023 Last updated: Feb 20, 2024	Publications: PubMed (3) PubMed: 25174816‚ 25967232‚ 28498829 Comment: This sequence change creates a premature translational stop signal (p.Val406Argfs2) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, … (more) This sequence change creates a premature translational stop signal (p.Val406Argfs2) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 138 amino acid(s) of the BTD protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BTD protein in which other variant(s) (p.Asp543Glu) have been determined to be pathogenic (PMID: 25174816, 25967232, 28498829). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with BTD-related conditions. This variant is not present in population databases (gnomAD no frequency). (less)

Comment:

This sequence change creates a premature translational stop signal (p.Val406Argfs*2) in the BTD gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 138 amino acid(s) of the BTD protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BTD protein in which other variant(s) (p.Asp543Glu) have been determined to be pathogenic (PMID: 25174816, 25967232, 28498829). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with BTD-related conditions. This variant is not present in population databases (gnomAD no frequency).

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
Biotinidase deficiency: Genotype-biochemical phenotype association in Brazilian patients.	Borsatto T	PloS one	2017	PMID: 28498829
High Incidence of Biotinidase Deficiency from a Pilot Newborn Screening Study in Minas Gerais, Brazil.	Lara MT	JIMD reports	2015	PMID: 25967232
Biotinidase deficiency: clinical and genetic studies of 38 Brazilian patients.	Borsatto T	BMC medical genetics	2014	PMID: 25174816

Text-mined citations for this variant ...

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001370658.1(BTD):c.1130_1155dup (p.Val386delinsArgTer)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...