rs13131655

Variant names:

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.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

Publications

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

EVC2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_147127.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.61).

BP6

Variant 4-5640547-T-C is Benign according to our data. Variant chr4-5640547-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147127.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC2	NM_147127.5	MANE Select	c.1437A>G	p.Glu479Glu	synonymous	Exon 10 of 22	NP_667338.3
	EVC2	NM_001166136.2		c.1197A>G	p.Glu399Glu	synonymous	Exon 10 of 22	NP_001159608.1	Q86UK5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EVC2	ENST00000344408.10	TSL:1 MANE Select	c.1437A>G	p.Glu479Glu	synonymous	Exon 10 of 22	ENSP00000342144.5	Q86UK5-1
EVC2	ENST00000310917.6	TSL:1	c.1197A>G	p.Glu399Glu	synonymous	Exon 10 of 22	ENSP00000311683.2	Q86UK5-2
EVC2	ENST00000475313.5	TSL:1	n.1197A>G		non_coding_transcript_exon	Exon 10 of 23	ENSP00000431981.1	A0A0C4DGE7

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

GnomAD2 exomes

AF:

0.192

AC:

48187

AN:

251396

AF XY:

0.188

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 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

African (AFR)

AF:

0.493

AC:

16496

AN:

33480

American (AMR)

AF:

0.135

AC:

6031

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

7479

AN:

26136

East Asian (EAS)

AF:

0.000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.154

AC:

13290

AN:

86256

European-Finnish (FIN)

AF:

0.167

AC:

8893

AN:

53410

Middle Eastern (MID)

AF:

0.333

AC:

1918

AN:

5768

European-Non Finnish (NFE)

AF:

0.198

AC:

220638

AN:

1111982

Other (OTH)

AF:

0.212

AC:

12795

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

14832

29664

44495

59327

74159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7624

15248

22872

30496

38120

<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:

0.269

AC:

40835

AN:

152006

Hom.:

6795

Cov.:

AF XY:

0.263

AC XY:

19535

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.473

AC:

19582

AN:

41392

American (AMR)

AF:

0.202

AC:

3083

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.279

AC:

968

AN:

3470

East Asian (EAS)

AF:

0.00232

AC:

AN:

5170

South Asian (SAS)

AF:

0.141

AC:

678

AN:

4818

European-Finnish (FIN)

AF:

0.166

AC:

1761

AN:

10596

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

13997

AN:

67964

Other (OTH)

AF:

0.259

AC:

547

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1396

2792

4189

5585

6981

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.250

Hom.:

6708

Bravo

AF:

0.279

Asia WGS

AF:

0.0980

AC:

342

AN:

3478

EpiCase

AF:

0.221

EpiControl

AF:

0.221

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Ellis-van Creveld syndrome (1)

Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.5

(source)

DANN

Benign

0.67

PhyloP100

-0.71

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over