NM_147127.5(EVC2):c.1364C>G (p.Thr455Arg) AND Ellis-van Creveld syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 12, 2018
Review status:: criteria provided, conflicting classifications

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:: RCV000680149.18

Allele description [Variation Report for NM_147127.5(EVC2):c.1364C>G (p.Thr455Arg)]

NM_147127.5(EVC2):c.1364C>G (p.Thr455Arg)

Genes:

LOC126806961:BRD4-independent group 4 enhancer GRCh37_chr4:5641443-5642642 [Gene]
EVC2:EvC ciliary complex subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.2

Genomic location:

Preferred name:

NM_147127.5(EVC2):c.1364C>G (p.Thr455Arg)

HGVS:

NC_000004.12:g.5640620G>C
NG_015821.1:g.73929C>G
NM_001166136.2:c.1124C>G
NM_147127.5:c.1364C>GMANE SELECT
NP_001159608.1:p.Thr375Arg
NP_667338.3:p.Thr455Arg
NC_000004.11:g.5642347G>C
NM_147127.4:c.1364C>G

Protein change:

T375R

Links:

dbSNP: rs141287105

NCBI 1000 Genomes Browser:

rs141287105

Molecular consequence:

NM_001166136.2:c.1124C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_147127.5:c.1364C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ellis-van Creveld syndrome (EVC)
Synonyms:: Chondroectodermal dysplasia; Mesoectodermal dysplasia
Identifiers:: MONDO: MONDO:0009162; MedGen: C0013903; Orphanet: 289; OMIM: 225500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000450093	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Jan 12, 2018)	germline	clinical testing	Citation Link,
SCV000807606	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 1, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25741868, 25326635

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000450093

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Likely benign
(Jan 12, 2018)

germline

clinical testing

Citation Link,

SCV000807606

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 1, 2017)

germline

clinical testing

PubMed (2)
[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	germline	unknown	not provided	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

Molecular findings among patients referred for clinical whole-exome sequencing.

Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, Ward P, Braxton A, Wang M, Buhay C, Veeraraghavan N, Hawes A, Chiang T, Leduc M, Beuten J, Zhang J, He W, Scull J, Willis A, Landsverk M, Craigen WJ, Bekheirnia MR, et al.

JAMA. 2014 Nov 12;312(18):1870-9. doi: 10.1001/jama.2014.14601.

PubMed [citation]

PMID:: 25326635
PMCID:: PMC4326249

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000450093.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

#	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

From Baylor Genetics, SCV000807606.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing (GTR000508680.4)	PubMed (2)

Description

This mutation was found once in our laboratory in trans with another variant in a 3-year-old male with ectodermal dysplasia. Heterozygotes would be expected to be asymptomatic carriers.

#	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	(GTR000508680.4)	not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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