NM_003640.5(ELP1):c.641del (p.Pro214fs) AND Familial dysautonomia

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Jun 30, 2021
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:: RCV000668489.5

Allele description [Variation Report for NM_003640.5(ELP1):c.641del (p.Pro214fs)]

NM_003640.5(ELP1):c.641del (p.Pro214fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

9q31.3

Genomic location:

Preferred name:

NM_003640.5(ELP1):c.641del (p.Pro214fs)

HGVS:

NC_000009.12:g.108919263del
NG_008788.1:g.20068del
NM_001318360.2:c.299del
NM_001330749.2:c.-307-1591del
NM_003640.5:c.641delMANE SELECT
NP_001305289.1:p.Pro100fs
NP_003631.2:p.Pro214fs
LRG_251t1:c.641del
LRG_251:g.20068del
NC_000009.11:g.111681541del
NC_000009.11:g.111681543del
NM_003640.3:c.641del
NM_003640.3:c.641delC
NM_003640.4:c.641del
NM_003640.4:c.641delC

Protein change:

P100fs

Links:

dbSNP: rs759412460

NCBI 1000 Genomes Browser:

rs759412460

Molecular consequence:

NM_001318360.2:c.299del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003640.5:c.641del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001330749.2:c.-307-1591del - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Name:: Familial dysautonomia (HSAN3)
Synonyms:: NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE III; HSAN III; Hereditary sensory and autonomic neuropathy 3; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009131; MedGen: C0013364; Orphanet: 1764; OMIM: 223900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000793102	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Jul 27, 2017)	unknown	clinical testing	Citation Link,
SCV000807810	GeneID Lab - Advanced Molecular Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 10, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001752551	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 30, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000793102

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Jul 27, 2017)

unknown

clinical testing

Citation Link,

SCV000807810

GeneID Lab - Advanced Molecular Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 10, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001752551

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 30, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

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	clinical testing
Caucasian	germline	no	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Counsyl, SCV000793102.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	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 GeneID Lab - Advanced Molecular Diagnostics, SCV000807810.1

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

Description

This variant deletes one nucleotide resulting in an amino acid alteration, replacing a proline (P) with a glutamine (Q) at codon 214 creating a premature stop signal in the new reading frame noted as p.P214Qfs*39. The substitution is predicted to result in a non-functional ELP1 protein, either through protein truncation or nonsense-mediated mRNA decay. This mutation is considered a non-tolerated amino acid change based on in silico prediction algorithms (disease causing), and it has not been reported in the Clinical Variant Database (NCBI National Library of Medicine, NIH) but it has been described in 7 alleles out of 119208, the majority (6) belonging to heterozygous carries of Latino origin. Based on these findings and the limited literature regarding this substitution we consider it as a likely pathogenic variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		1	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV001752551.1

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

#	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

Last Updated: Nov 24, 2024

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