NM_003640.5(ELP1):c.2204+6T>C AND not specified

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 9, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV004018577.1

Allele description [Variation Report for NM_003640.5(ELP1):c.2204+6T>C]

NM_003640.5(ELP1):c.2204+6T>C

Gene:

ELP1:elongator acetyltransferase complex subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q31.3

Genomic location:

Preferred name:

NM_003640.5(ELP1):c.2204+6T>C

HGVS:

NC_000009.12:g.108899816A>G
NG_008788.1:g.39513T>C
NM_001318360.2:c.1862+6T>C
NM_001330749.2:c.1157+6T>C
NM_003640.4(ELP1):c.2204+6T>C
NM_003640.5:c.2204+6T>CMANE SELECT
LRG_251t1:c.2204+6T>C
LRG_251:g.39513T>C
NC_000009.11:g.111662096A>G
NM_003640.3:c.2204+6T>C
NM_003640.4(ELP1):c.2204+6T>C
NM_003640.4:c.2204+6T>C
c.2204+6T>C (p.?)

Nucleotide change:

IVS20DS, T-C, +6

Links:

OMIM: 603722.0001; dbSNP: rs111033171

NCBI 1000 Genomes Browser:

rs111033171

Molecular consequence:

NM_001318360.2:c.1862+6T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001330749.2:c.1157+6T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_003640.5:c.2204+6T>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002754700	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Nov 9, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11179008, 11179021, 16964593, 22190446, 29762696 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002754700

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Nov 9, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia.

Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco MP, Liebert CB, Chadwick B, Idelson M, Reznik L, Robbins C, Makalowska I, Brownstein M, Krappmann D, Scheidereit C, Maayan C, Axelrod FB, Gusella JF.

Am J Hum Genet. 2001 Mar;68(3):598-605. Epub 2001 Jan 22.

PubMed [citation]

PMID:: 11179008
PMCID:: PMC1274473

Familial dysautonomia is caused by mutations of the IKAP gene.

Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, Ekstein J, Rubin BY.

Am J Hum Genet. 2001 Mar;68(3):753-8. Epub 2001 Jan 22.

PubMed [citation]

PMID:: 11179021
PMCID:: PMC1274486

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV002754700.3

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

Description

The c.2204+6T>C intronic alteration consists of a T to C substitution 6 nucleotides after exon 20 (coding exon 19) of the IKBKAP gene. This alteration is also designated as c.2507+6T>C or IVS20+6T>C in the published literature. Based on data from gnomAD, the C allele has an overall frequency of 0.062% (174/282646) total alleles studied. The highest observed frequency was 1.341% (139/10364) of Ashkenazi Jewish alleles. This alteration has been reported in the homozygous state in multiple unrelated individuals with familial dysautonomia (FD) and is reported to be the most common pathogenic alteration associated with this condition (Slaugenhaupt, 2001; Anderson, 2001; Boone, 2012). This nucleotide position is well conserved in available vertebrate species. Skipping of exon 20, which is predicted to result in a frameshift, was detected in brain tissue from an individual affected with FD as well as in fibroblasts derived from multiple FD patients (Slaugenhaupt, 2001; Boone, 2012; Bruun, 2018; Ibrahim, 2007). Based on the available evidence, this alteration is 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: Oct 26, 2024

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