rs10025164

Positions:

• chr4-5615568-T-C
• chr4-5615568-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_147127.5(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 NM_147127.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.08

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]

ACMG classification

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	UniProt
EVC2	NM_147127.5	c.2707-24A>G		intron_variant		ENST00000344408.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC2	ENST00000344408.10	c.2707-24A>G		intron_variant		1	NM_147127.5	P2
EVC2	ENST00000310917.6	c.2467-24A>G		intron_variant		1		A2
EVC2	ENST00000475313.5	c.2467-24A>G		intron_variant, NMD_transcript_variant		1
EVC2	ENST00000509670.1	c.*1100-24A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56412 AN: 151884 Hom.: 11590 Cov.: 32

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

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.: 39 AF XY: 0.294 AC XY: 213853 AN XY: 727094

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.: 32 AF XY: 0.376 AC XY: 27978 AN XY: 74312

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2018

- -

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

Other links and lift over

dbSNP: rs10025164; hg19: chr4-5617295;