rs60809236

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_147127.5(EVC2):c.3023C>T(p.Ser1008Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,613,748 control chromosomes in the GnomAD database, including 498 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1008W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.032 ( 258 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 240 hom. )

Consequence

EVC2
NM_147127.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.30

Publications

5 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022625625).

BP6

Variant 4-5584657-G-A is Benign according to our data. Variant chr4-5584657-G-A is described in ClinVar as Benign. ClinVar VariationId is 262615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC2	NM_147127.5 link	c.3023C>T	p.Ser1008Leu	missense_variant	Exon 17 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.3023C>T	p.Ser1008Leu	missense_variant	Exon 17 of 22	1	NM_147127.5	ENSP00000342144.5		Q86UK5-1

Frequencies

GnomAD3 genomes

AF:

0.0318

AC:

4836

AN:

152046

Hom.:

254

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000514

Gnomad OTH

AF:

0.0291

GnomAD2 exomes

AF:

0.00903

AC:

2261

AN:

250334

AF XY:

0.00658

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.00779

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000575

Gnomad OTH exome

AF:

0.00572

GnomAD4 exome

AF:

0.00351

AC:

5124

AN:

1461584

Hom.:

240

Cov.:

AF XY:

0.00314

AC XY:

2283

AN XY:

727058

show subpopulations

African (AFR)

AF:

0.113

AC:

3781

AN:

33476

American (AMR)

AF:

0.00852

AC:

381

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.000267

AC:

AN:

86148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00971

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000346

AC:

385

AN:

1111904

Other (OTH)

AF:

0.00821

AC:

496

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

292

584

877

1169

1461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<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:

0.0319

AC:

4856

AN:

152164

Hom.:

258

Cov.:

AF XY:

0.0306

AC XY:

2276

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.109

AC:

4509

AN:

41462

American (AMR)

AF:

0.0141

AC:

216

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000416

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000515

AC:

AN:

68020

Other (OTH)

AF:

0.0288

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

217

435

652

870

1087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0113

Hom.:

179

Bravo

AF:

0.0377

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.104

AC:

458

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0110

AC:

1339

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000713

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 14, 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;C0457013:Curry-Hall syndrome

Benign:1

Jan 30, 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

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.050

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.41

N;.

PhyloP100

1.3

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.14

Sift

Benign

0.34

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.014

B;.

Vest4

0.045

MPC

0.020

ClinPred

0.0076

GERP RS

-0.13

Varity_R

0.052

gMVP

0.086

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