NM_002225.5(IVD):c.457-3_457-2delinsGG AND Isovaleryl-CoA dehydrogenase deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 7, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000169022.8

Allele description [Variation Report for NM_002225.5(IVD):c.457-3_457-2delinsGG]

NM_002225.5(IVD):c.457-3_457-2delinsGG

Gene:

IVD:isovaleryl-CoA dehydrogenase [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

15q15.1

Genomic location:

Preferred name:

NM_002225.5(IVD):c.457-3_457-2delinsGG

HGVS:

NC_000015.10:g.40411257_40411258delinsGG
NG_011986.2:g.10773_10774delinsGG
NM_001159508.3:c.367-3_367-2delinsGG
NM_001354597.3:c.409-3_409-2delinsGG
NM_001354598.3:c.457-3_457-2delinsGG
NM_001354599.3:c.544-3_544-2delinsGG
NM_001354600.3:c.544-3_544-2delinsGG
NM_001354601.3:c.457-3_457-2delinsGG
NM_002225.5:c.457-3_457-2delinsGGMANE SELECT
NC_000015.9:g.40703456_40703457delinsGG
NM_002225.3:c.466-3_466-2delCAinsGG
NM_002225.3:c.466-3_466-2delinsGG

Links:

dbSNP: rs786204427

NCBI 1000 Genomes Browser:

rs786204427

Molecular consequence:

NM_001159508.3:c.367-3_367-2delinsGG - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354597.3:c.409-3_409-2delinsGG - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354598.3:c.457-3_457-2delinsGG - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354599.3:c.544-3_544-2delinsGG - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354600.3:c.544-3_544-2delinsGG - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001354601.3:c.457-3_457-2delinsGG - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_002225.5:c.457-3_457-2delinsGG - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Isovaleryl-CoA dehydrogenase deficiency (IVA)
Synonyms:: Isovaleric acid CoA dehydrogenase deficiency; Isovaleric acidemia; Isovaleryl CoA carboxylase deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009475; MedGen: C0268575; Orphanet: 33; OMIM: 243500

Recent activity

Clear Turn Off Turn On

Homologene neighbors for GEO Profiles (Select 78961662) (0)
GEO Profiles
Gene Links for GEO Profiles (Select 78959557) (1)
Gene
MTDH metadherin [Homo sapiens]
MTDH metadherin [Homo sapiens]
Gene ID:92140

Gene
Related DataSets for GEO Profiles (Select 116777443) (1)
GEO DataSets
Ruptured intracranial aneurysms
Ruptured intracranial aneurysms
Accession: GDS5186

GEO DataSets

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000220169	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Mar 18, 2014)	unknown	literature only	PubMed (3) [See all records that cite these PMIDs] 10677295, 17576084, 22004070 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV001402877	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 7, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 16602101, 17576084, 22004070, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000220169

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(Mar 18, 2014)

unknown

literature only

PubMed (3)
[See all records that cite these PMIDs]

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV001402877

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 7, 2023)

germline

clinical testing

PubMed (5)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Exon skipping in IVD RNA processing in isovaleric acidemia caused by point mutations in the coding region of the IVD gene.

Vockley J, Rogan PK, Anderson BD, Willard J, Seelan RS, Smith DI, Liu W.

Am J Hum Genet. 2000 Feb;66(2):356-67.

PubMed [citation]

PMID:: 10677295
PMCID:: PMC1288088

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000220169.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV001402877.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects a splice site in intron 4 of the IVD gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IVD are known to be pathogenic (PMID: 16602101). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. Disruption of this splice site has been observed in individuals with isovaleric acidemia (PMID: 17576084, 22004070; Invitae). This variant is also known as c.457‚Äì3_2CA>GG. ClinVar contains an entry for this variant (Variation ID: 188724). 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: Jun 23, 2024

ClinVar

Relating variation to medicine