NM_018100.4(EFHC1):c.1586C>A (p.Ala529Glu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 14, 2019
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:: RCV003766605.2

Allele description [Variation Report for NM_018100.4(EFHC1):c.1586C>A (p.Ala529Glu)]

NM_018100.4(EFHC1):c.1586C>A (p.Ala529Glu)

Gene:

EFHC1:EF-hand domain containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p12.2

Genomic location:

Preferred name:

NM_018100.4(EFHC1):c.1586C>A (p.Ala529Glu)

HGVS:

NC_000006.12:g.52479733C>A
NG_016760.1:g.64538C>A
NM_001172420.2:c.1529C>A
NM_018100.4:c.1586C>AMANE SELECT
NP_001165891.1:p.Ala510Glu
NP_060570.2:p.Ala529Glu
NC_000006.11:g.52344531C>A
NM_018100.3:c.1586C>A
NR_033327.2:n.2912C>A

Protein change:

A510E

Links:

dbSNP: rs759944784

NCBI 1000 Genomes Browser:

rs759944784

Molecular consequence:

NM_001172420.2:c.1529C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_018100.4:c.1586C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_033327.2:n.2912C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Absence seizure
Synonyms:: Absence epilepsy
Identifiers:: MONDO: MONDO:0850093; MedGen: C0014553; Orphanet: 1941

Name:: Myoclonic epilepsy, juvenile, susceptibility to, 1
Synonyms:: Myoclonic Epilepsy, Juvenile, 1; EJM1
Identifiers:: MONDO: MONDO:0020752; MedGen: C1850778; OMIM: 254770

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000552791	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 14, 2019)	germline	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

SCV000552791

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 14, 2019)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000552791.7

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

Description

In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a EFHC1-related disease. This sequence change replaces alanine with glutamic acid at codon 529 of the EFHC1 protein (p.Ala529Glu). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and glutamic acid.

#	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 13, 2024

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