Variant rs10025164 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000344408.10(EVC2):c.2707-24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,613,586 control chromosomes in the GnomAD database, including 79,575 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11609 hom., cov: 32)

Exomes 𝑓: 0.30 ( 67966 hom. )

Consequence

EVC2
ENST00000344408.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.08

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=-0.89).

BP6

Variant 4-5615568-T-C is Benign according to our data. Variant chr4-5615568-T-C is described in ClinVar as [Benign]. Clinvar id is 262614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVC2	NM_147127.5 linkuse as main transcript	c.2707-24A>G		intron_variant		ENST00000344408.10	NP_667338.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
EVC2	ENST00000344408.10 linkuse as main transcript	c.2707-24A>G	intron_variant	1	NM_147127.5	ENSP00000342144	P2	Q86UK5-1
EVC2	ENST00000310917.6 linkuse as main transcript	c.2467-24A>G	intron_variant	1		ENSP00000311683	A2	Q86UK5-2
EVC2	ENST00000475313.5 linkuse as main transcript	c.2467-24A>G	intron_variant, NMD_transcript_variant	1		ENSP00000431981
EVC2	ENST00000509670.1 linkuse as main transcript	c.*1100-24A>G	intron_variant, NMD_transcript_variant	1		ENSP00000423876

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56412

AN:

151884

Hom.:

11590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.533

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.375

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.292

Gnomad FIN

AF:

0.348

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.335

GnomAD3 exomes

AF:

0.344

AC:

86576

AN:

251354

Hom.:

16418

AF XY:

0.334

AC XY:

45380

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.534

Gnomad AMR exome

AF:

0.405

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.627

Gnomad SAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.340

Gnomad NFE exome

AF:

0.280

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.296

AC:

432171

AN:

1461582

Hom.:

67966

Cov.:

AF XY:

0.294

AC XY:

213853

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.542

Gnomad4 AMR exome

AF:

0.400

Gnomad4 ASJ exome

AF:

0.257

Gnomad4 EAS exome

AF:

0.598

Gnomad4 SAS exome

AF:

0.280

Gnomad4 FIN exome

AF:

0.337

Gnomad4 NFE exome

AF:

0.273

Gnomad4 OTH exome

AF:

0.310

GnomAD4 genome

AF:

0.371

AC:

56455

AN:

152004

Hom.:

11609

Cov.:

AF XY:

0.376

AC XY:

27978

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.533

Gnomad4 AMR

AF:

0.374

Gnomad4 ASJ

AF:

0.255

Gnomad4 EAS

AF:

0.603

Gnomad4 SAS

AF:

0.292

Gnomad4 FIN

AF:

0.348

Gnomad4 NFE

AF:

0.273

Gnomad4 OTH

AF:

0.330

Alfa

AF:

0.317

Hom.:

1545

Bravo

AF:

0.387

Asia WGS

AF:

0.451

AC:

1567

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 25, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.066

DANN

Benign

0.34

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

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