NM_147127.5:c.1437A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_147127.5(EVC2):c.1437A>G(p.Glu479Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,613,854 control chromosomes in the GnomAD database, including 38,314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6795 hom., cov: 31)

Exomes 𝑓: 0.20 ( 31519 hom. )

Consequence

EVC2
NM_147127.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.707

Variant links:

Genes affected

EVC2 (HGNC:19747): (EvC ciliary complex subunit 2) This gene encodes a protein that functions in bone formation and skeletal development. Mutations in this gene, as well as in a neighboring gene that lies in a head-to-head configuration, cause Ellis-van Creveld syndrome, an autosomal recessive skeletal dysplasia that is also known as chondroectodermal dysplasia. Mutations in this gene also cause acrofacial dysostosis Weyers type, also referred to as Curry-Hall syndrome, a disease that combines limb and facial abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

EVC2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 4-5640547-T-C is Benign according to our data. Variant chr4-5640547-T-C is described in ClinVar as [Benign]. Clinvar id is 193763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.707 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC2	NM_147127.5 link	c.1437A>G	p.Glu479Glu	synonymous_variant	Exon 10 of 22	ENST00000344408.10	NP_667338.3	Q86UK5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EVC2	ENST00000344408.10 link	c.1437A>G	p.Glu479Glu	synonymous_variant	Exon 10 of 22	1	NM_147127.5	ENSP00000342144.5	Q86UK5-1
EVC2	ENST00000310917.6 link	c.1197A>G	p.Glu399Glu	synonymous_variant	Exon 10 of 22	1		ENSP00000311683.2	Q86UK5-2
EVC2	ENST00000475313.5 link	n.1197A>G		non_coding_transcript_exon_variant	Exon 10 of 23	1		ENSP00000431981.1	A0A0C4DGE7
EVC2	ENST00000509670.1 link	n.1197A>G		non_coding_transcript_exon_variant	Exon 11 of 23	1		ENSP00000423876.1	E9PFT2

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40787

AN:

151888

Hom.:

6775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.262

GnomAD3 exomes

AF:

0.192

AC:

48187

AN:

251396

Hom.:

5941

AF XY:

0.188

AC XY:

25597

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.479

Gnomad AMR exome

AF:

0.127

Gnomad ASJ exome

AF:

0.299

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.150

Gnomad FIN exome

AF:

0.167

Gnomad NFE exome

AF:

0.206

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.197

AC:

287570

AN:

1461848

Hom.:

31519

Cov.:

AF XY:

0.196

AC XY:

142632

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.493

Gnomad4 AMR exome

AF:

0.135

Gnomad4 ASJ exome

AF:

0.286

Gnomad4 EAS exome

AF:

0.000756

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.198

Gnomad4 OTH exome

AF:

0.212

GnomAD4 genome

AF:

0.269

AC:

40835

AN:

152006

Hom.:

6795

Cov.:

AF XY:

0.263

AC XY:

19535

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.473

Gnomad4 AMR

AF:

0.202

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.141

Gnomad4 FIN

AF:

0.166

Gnomad4 NFE

AF:

0.206

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.233

Hom.:

4158

Bravo

AF:

0.279

Asia WGS

AF:

0.0980

AC:

342

AN:

3478

EpiCase

AF:

0.221

EpiControl

AF:

0.221

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 21, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jul 07, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ellis-van Creveld syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.5

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over