NM_153717.3(EVC):c.1448C>T (p.Pro483Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 12, 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:: RCV000547448.3

Allele description [Variation Report for NM_153717.3(EVC):c.1448C>T (p.Pro483Leu)]

NM_153717.3(EVC):c.1448C>T (p.Pro483Leu)

Gene:

EVC:EvC ciliary complex subunit 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.2

Genomic location:

Preferred name:

NM_153717.3(EVC):c.1448C>T (p.Pro483Leu)

HGVS:

NC_000004.12:g.5753917C>T
NG_008843.1:g.47721C>T
NM_001306090.2:c.1448C>T
NM_001306092.2:c.1448C>T
NM_153717.3:c.1448C>TMANE SELECT
NP_001293019.1:p.Pro483Leu
NP_001293021.1:p.Pro483Leu
NP_714928.1:p.Pro483Leu
NC_000004.11:g.5755644C>T
NM_153717.2:c.1448C>T

Protein change:

P483L

Links:

dbSNP: rs376440801

NCBI 1000 Genomes Browser:

rs376440801

Molecular consequence:

NM_001306090.2:c.1448C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001306092.2:c.1448C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153717.3:c.1448C>T - 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

Name:: Curry-Hall syndrome (WAD)
Synonyms:: Acrofacial dysostosis of Weyers; WEYERS ACRODENTAL DYSOSTOSIS
Identifiers:: MONDO: MONDO:0008673; MedGen: C0457013; Orphanet: 952; OMIM: 193530

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000634717	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 12, 2022)	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

SCV000634717

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 12, 2022)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000634717.2

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

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 483 of the EVC protein (p.Pro483Leu). This variant is present in population databases (rs376440801, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with EVC-related conditions. ClinVar contains an entry for this variant (Variation ID: 461813). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Dec 24, 2023

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