rs12511039

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_147127.5(EVC2):c.3507C>T(p.His1169His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,583,144 control chromosomes in the GnomAD database, including 96,128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8194 hom., cov: 30)

Exomes 𝑓: 0.33 ( 87934 hom. )

Consequence

EVC2
NM_147127.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.586

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=-0.83).

BP6

Variant 4-5568494-G-A is Benign according to our data. Variant chr4-5568494-G-A is described in ClinVar as [Benign]. Clinvar id is 195539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5568494-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.586 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC2	NM_147127.5 link	c.3507C>T	p.His1169His	synonymous_variant	Exon 20 of 22	ENST00000344408.10	NP_667338.3	Q86UK5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC2	ENST00000344408.10 link	c.3507C>T	p.His1169His	synonymous_variant	Exon 20 of 22	1	NM_147127.5	ENSP00000342144.5		Q86UK5-1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45734

AN:

151480

Hom.:

8176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.194

Gnomad AMR

AF:

0.354

Gnomad ASJ

AF:

0.311

Gnomad EAS

AF:

0.863

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.303

Gnomad OTH

AF:

0.304

GnomAD3 exomes

AF:

0.391

AC:

81988

AN:

209712

Hom.:

18777

AF XY:

0.398

AC XY:

44959

AN XY:

113064

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.421

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.865

Gnomad SAS exome

AF:

0.528

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.346

GnomAD4 exome

AF:

0.332

AC:

474823

AN:

1431546

Hom.:

87934

Cov.:

AF XY:

0.338

AC XY:

240155

AN XY:

709972

show subpopulations

Gnomad4 AFR exome

AF:

0.175

Gnomad4 AMR exome

AF:

0.413

Gnomad4 ASJ exome

AF:

0.303

Gnomad4 EAS exome

AF:

0.875

Gnomad4 SAS exome

AF:

0.519

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.300

Gnomad4 OTH exome

AF:

0.341

GnomAD4 genome

AF:

0.302

AC:

45772

AN:

151598

Hom.:

8194

Cov.:

AF XY:

0.313

AC XY:

23171

AN XY:

74044

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.354

Gnomad4 ASJ

AF:

0.311

Gnomad4 EAS

AF:

0.863

Gnomad4 SAS

AF:

0.537

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.303

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.310

Hom.:

14345

Bravo

AF:

0.301

Asia WGS

AF:

0.679

AC:

2359

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

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

- -

Jun 23, 2014

Eurofins Ntd Llc (ga)

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. -

Ellis-van Creveld syndrome

Benign:2

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. -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Curry-Hall syndrome

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

DANN

Benign

0.43

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