rs16837501

Positions:

chr4-5622551-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_147127.5(EVC2):c.2487G>A(p.Glu829=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,613,874 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 39 hom. )

Consequence

EVC2
NM_147127.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.53

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 4-5622551-C-T is Benign according to our data. Variant chr4-5622551-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 262612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-5622551-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.53 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00212 (322/152186) while in subpopulation EAS AF= 0.0341 (175/5136). AF 95% confidence interval is 0.0299. There are 3 homozygotes in gnomad4. There are 202 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVC2	NM_147127.5 linkuse as main transcript	c.2487G>A	p.Glu829=	synonymous_variant	14/22	ENST00000344408.10	NP_667338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVC2	ENST00000344408.10 linkuse as main transcript	c.2487G>A	p.Glu829=	synonymous_variant	14/22	1	NM_147127.5	ENSP00000342144	P2	Q86UK5-1
EVC2	ENST00000310917.6 linkuse as main transcript	c.2247G>A	p.Glu749=	synonymous_variant	14/22	1		ENSP00000311683	A2	Q86UK5-2
EVC2	ENST00000475313.5 linkuse as main transcript	c.2247G>A	p.Glu749=	synonymous_variant, NMD_transcript_variant	14/23	1		ENSP00000431981
EVC2	ENST00000509670.1 linkuse as main transcript	c.*880G>A		3_prime_UTR_variant, NMD_transcript_variant	15/23	1		ENSP00000423876

Frequencies

GnomAD3 genomes

AF:

0.00211

AC:

321

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0338

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00801

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00402

AC:

1006

AN:

250056

Hom.:

AF XY:

0.00371

AC XY:

502

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.0385

Gnomad SAS exome

AF:

0.000983

Gnomad FIN exome

AF:

0.00720

Gnomad NFE exome

AF:

0.000789

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00154

AC:

2253

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

1133

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.0315

Gnomad4 SAS exome

AF:

0.00149

Gnomad4 FIN exome

AF:

0.00756

Gnomad4 NFE exome

AF:

0.000287

Gnomad4 OTH exome

AF:

0.00220

GnomAD4 genome

AF:

0.00212

AC:

322

AN:

152186

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

202

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.0341

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00801

Gnomad4 NFE

AF:

0.000574

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000521

Hom.:

Bravo

AF:

0.00187

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 24, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Ellis-van Creveld syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.99

DANN

Benign

0.36

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