rs137852928

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_147127.5(EVC2):c.2848C>T(p.Arg950Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R950R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

EVC2
NM_147127.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts P:1U:6

Conservation

PhyloP100: 1.23

Publications

10 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: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.755

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.2848C>T	p.Arg950Trp	missense	Exon 17 of 22	NP_667338.3
	EVC2	NM_001166136.2		c.2608C>T	p.Arg870Trp	missense	Exon 17 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.2848C>T	p.Arg950Trp	missense	Exon 17 of 22	ENSP00000342144.5	Q86UK5-1
EVC2	ENST00000310917.6	TSL:1	c.2608C>T	p.Arg870Trp	missense	Exon 17 of 22	ENSP00000311683.2	Q86UK5-2
EVC2	ENST00000475313.5	TSL:1	n.2608C>T		non_coding_transcript_exon	Exon 17 of 23	ENSP00000431981.1	A0A0C4DGE7

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000163

AC:

AN:

251302

AF XY:

0.000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000129

AC:

189

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

100

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.000313

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00233

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.000104

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000764

AC:

AN:

1112010

Other (OTH)

AF:

0.000232

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000125

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41436

American (AMR)

AF:

0.000196

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000174

Hom.:

Bravo

AF:

0.000110

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Ellis-van Creveld syndrome (3)

Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (2)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Benign

-0.040

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.24

LIST_S2

Uncertain

0.86

M_CAP

Uncertain

0.088

MetaRNN

Pathogenic

0.75

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.5

PhyloP100

1.2

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.53

Sift

Benign

0.045

Sift4G

Uncertain

0.025

Varity_R

0.22

gMVP

0.18

Mutation Taster

=10/90

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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