4-5708528-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_147127.5(EVC2):c.-15G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 1,433,358 control chromosomes in the GnomAD database, including 5,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 585 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5157 hom. )

Consequence

EVC2
NM_147127.5 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.62

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-5708528-C-T is Benign according to our data. Variant chr4-5708528-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5708528-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC2	NM_147127.5 link	c.-15G>A		5_prime_UTR_variant	Exon 1 of 22	ENST00000344408.10	NP_667338.3	Q86UK5-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EVC2	ENST00000344408.10 link	c.-15G>A	5_prime_UTR_variant	Exon 1 of 22	1	NM_147127.5	ENSP00000342144.5	Q86UK5-1
EVC2	ENST00000310917.6 link	c.-13+301G>A	intron_variant	Intron 1 of 21	1		ENSP00000311683.2	Q86UK5-2
EVC2	ENST00000475313.5 link	n.-13+301G>A	intron_variant	Intron 1 of 22	1		ENSP00000431981.1	A0A0C4DGE7
EVC2	ENST00000509670.1 link	n.-107+301G>A	intron_variant	Intron 1 of 22	1		ENSP00000423876.1	E9PFT2

Frequencies

GnomAD3 genomes

AF:

0.0757

AC:

11509

AN:

152036

Hom.:

585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0744

Gnomad MID

AF:

0.175

Gnomad NFE

AF:

0.0782

Gnomad OTH

AF:

0.0876

GnomAD3 exomes

AF:

0.133

AC:

6690

AN:

50152

Hom.:

475

AF XY:

0.131

AC XY:

3915

AN XY:

29908

show subpopulations

Gnomad AFR exome

AF:

0.0405

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.259

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.0815

Gnomad NFE exome

AF:

0.0865

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.0842

AC:

107897

AN:

1281208

Hom.:

5157

Cov.:

AF XY:

0.0853

AC XY:

53665

AN XY:

628894

show subpopulations

Gnomad4 AFR exome

AF:

0.0278

Gnomad4 AMR exome

AF:

0.154

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.144

Gnomad4 FIN exome

AF:

0.0750

Gnomad4 NFE exome

AF:

0.0765

Gnomad4 OTH exome

AF:

0.0909

GnomAD4 genome

AF:

0.0756

AC:

11505

AN:

152150

Hom.:

585

Cov.:

AF XY:

0.0777

AC XY:

5781

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0275

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.218

Gnomad4 SAS

AF:

0.128

Gnomad4 FIN

AF:

0.0744

Gnomad4 NFE

AF:

0.0782

Gnomad4 OTH

AF:

0.0866

Alfa

AF:

0.0317

Hom.:

Bravo

AF:

0.0807

Asia WGS

AF:

0.143

AC:

497

AN:

3472

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 21, 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. -

Mar 15, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ellis-van Creveld syndrome

Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Curry-Hall syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.15

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over