rs60121553

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_147127.5(EVC2):c.2235A>G(p.Glu745Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,613,900 control chromosomes in the GnomAD database, including 2,813 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 1437 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1376 hom. )

Consequence

EVC2
NM_147127.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.17

Publications

3 publications found

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 Gene-Disease associations (from GenCC):

acrofacial dysostosis, Weyers type
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
Ellis-van Creveld syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Laboratory for Molecular Medicine

EVC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 4-5622803-T-C is Benign according to our data. Variant chr4-5622803-T-C is described in ClinVar as Benign. ClinVar VariationId is 262611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.16 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC2	NM_147127.5 link	c.2235A>G	p.Glu745Glu	synonymous_variant	Exon 14 of 22	ENST00000344408.10	NP_667338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC2	ENST00000344408.10 link	c.2235A>G	p.Glu745Glu	synonymous_variant	Exon 14 of 22	1	NM_147127.5	ENSP00000342144.5

Frequencies

GnomAD3 genomes

AF:

0.0784

AC:

11907

AN:

151900

Hom.:

1436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.0409

Gnomad ASJ

AF:

0.00635

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.0578

GnomAD2 exomes

AF:

0.0248

AC:

6242

AN:

251330

AF XY:

0.0194

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.0211

Gnomad ASJ exome

AF:

0.00675

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000785

Gnomad NFE exome

AF:

0.00852

Gnomad OTH exome

AF:

0.0210

GnomAD4 exome

AF:

0.0149

AC:

21815

AN:

1461882

Hom.:

1376

Cov.:

AF XY:

0.0137

AC XY:

9985

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.263

AC:

8807

AN:

33480

American (AMR)

AF:

0.0231

AC:

1033

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00662

AC:

173

AN:

26136

East Asian (EAS)

AF:

0.000151

AC:

AN:

39700

South Asian (SAS)

AF:

0.00298

AC:

257

AN:

86258

European-Finnish (FIN)

AF:

0.00114

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.0378

AC:

218

AN:

5768

European-Non Finnish (NFE)

AF:

0.00868

AC:

9652

AN:

1112010

Other (OTH)

AF:

0.0266

AC:

1608

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1544

3088

4632

6176

7720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

504

1008

1512

2016

2520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0785

AC:

11931

AN:

152018

Hom.:

1437

Cov.:

AF XY:

0.0749

AC XY:

5566

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.255

AC:

10550

AN:

41382

American (AMR)

AF:

0.0408

AC:

623

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00635

AC:

AN:

3466

East Asian (EAS)

AF:

0.000389

AC:

AN:

5144

South Asian (SAS)

AF:

0.00290

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00815

AC:

554

AN:

68002

Other (OTH)

AF:

0.0572

AC:

121

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

460

919

1379

1838

2298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0440

Hom.:

375

Bravo

AF:

0.0910

Asia WGS

AF:

0.0310

AC:

107

AN:

3478

EpiCase

AF:

0.00971

EpiControl

AF:

0.0108

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jun 06, 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. -

PreventionGenetics, part of Exact Sciences

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

- -

Ellis-van Creveld syndrome

Benign:1

Jan 12, 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. -

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

-0.69

CADD

Benign

7.7

(source)

DANN

Benign

0.46

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over