4-5628743-TAA-TAAAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_147127.5(EVC2):c.1711-11_1711-10dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.091 ( 1107 hom., cov: 0)

Exomes 𝑓: 0.040 ( 318 hom. )

Consequence

EVC2
NM_147127.5 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:5

Conservation

PhyloP100: -0.151

Publications

4 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 -9 ACMG points.

BP6

Variant 4-5628743-T-TAA is Benign according to our data. Variant chr4-5628743-T-TAA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 349081.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC2	NM_147127.5 link	c.1711-11_1711-10dupTT		intron_variant	Intron 11 of 21	ENST00000344408.10	NP_667338.3	Q86UK5-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EVC2	ENST00000344408.10 link	c.1711-11_1711-10dupTT	intron_variant	Intron 11 of 21	1	NM_147127.5	ENSP00000342144.5	Q86UK5-1
EVC2	ENST00000310917.6 link	c.1471-11_1471-10dupTT	intron_variant	Intron 11 of 21	1		ENSP00000311683.2	Q86UK5-2
EVC2	ENST00000475313.5 link	n.1471-11_1471-10dupTT	intron_variant	Intron 11 of 22	1		ENSP00000431981.1	A0A0C4DGE7
EVC2	ENST00000509670.1 link	n.104-11_104-10dupTT	intron_variant	Intron 12 of 22	1		ENSP00000423876.1	E9PFT2

Frequencies

GnomAD3 genomes

AF:

0.0912

AC:

13554

AN:

148592

Hom.:

1101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.0629

Gnomad AMR

AF:

0.0521

Gnomad ASJ

AF:

0.0211

Gnomad EAS

AF:

0.000196

Gnomad SAS

AF:

0.00878

Gnomad FIN

AF:

0.0789

Gnomad MID

AF:

0.0732

Gnomad NFE

AF:

0.0413

Gnomad OTH

AF:

0.0706

GnomAD2 exomes

AF:

0.0507

AC:

9529

AN:

187796

AF XY:

0.0473

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.0349

Gnomad ASJ exome

AF:

0.0302

Gnomad EAS exome

AF:

0.0000624

Gnomad FIN exome

AF:

0.0809

Gnomad NFE exome

AF:

0.0484

Gnomad OTH exome

AF:

0.0451

GnomAD4 exome

AF:

0.0404

AC:

51202

AN:

1268394

Hom.:

318

Cov.:

AF XY:

0.0393

AC XY:

24823

AN XY:

631496

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.198

AC:

6242

AN:

31480

American (AMR)

AF:

0.0327

AC:

1303

AN:

39830

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

565

AN:

22372

East Asian (EAS)

AF:

0.0000836

AC:

AN:

35880

South Asian (SAS)

AF:

0.00748

AC:

558

AN:

74562

European-Finnish (FIN)

AF:

0.0654

AC:

3003

AN:

45904

Middle Eastern (MID)

AF:

0.0645

AC:

325

AN:

5042

European-Non Finnish (NFE)

AF:

0.0384

AC:

36873

AN:

960798

Other (OTH)

AF:

0.0444

AC:

2330

AN:

52526

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.388

Heterozygous variant carriers

2130

4260

6390

8520

10650

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1374

2748

4122

5496

6870

<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:

0.0913

AC:

13577

AN:

148700

Hom.:

1107

Cov.:

AF XY:

0.0919

AC XY:

6659

AN XY:

72466

show subpopulations

African (AFR)

AF:

0.219

AC:

8939

AN:

40908

American (AMR)

AF:

0.0520

AC:

780

AN:

14986

Ashkenazi Jewish (ASJ)

AF:

0.0211

AC:

AN:

3412

East Asian (EAS)

AF:

0.000196

AC:

AN:

5096

South Asian (SAS)

AF:

0.00902

AC:

AN:

4654

European-Finnish (FIN)

AF:

0.0789

AC:

765

AN:

9698

Middle Eastern (MID)

AF:

0.0753

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0413

AC:

2758

AN:

66716

Other (OTH)

AF:

0.0693

AC:

142

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

539

1079

1618

2158

2697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0357

Hom.:

399

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Aug 26, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 28, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 02, 2014

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Ellis-van Creveld syndrome

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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