rs60896170

chr4-5622496-C-T

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.2501+41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,598,712 control chromosomes in the GnomAD database, including 3,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (1408 hom., cov: 32)
  • Exomes 𝑓: 0.039 (2083 hom.)
• Consequence: EVC2 NM_147127.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.29

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=-1.01).
• BP6: Variant 4-5622496-C-T is Benign according to our data. Variant chr4-5622496-C-T is described in ClinVar as [Benign]. Clinvar id is 262613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EVC2	NM_147127.5	c.2501+41G>A		intron_variant		ENST00000344408.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EVC2	ENST00000344408.10	c.2501+41G>A		intron_variant		1	NM_147127.5	P2
EVC2	ENST00000310917.6	c.2261+41G>A		intron_variant		1		A2
EVC2	ENST00000475313.5	c.2261+41G>A		intron_variant, NMD_transcript_variant		1
EVC2	ENST00000509670.1	c.*894+41G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14752 AN: 151846 Hom.: 1405 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0509

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00872

Gnomad FIN AF: 0.0784

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0779

GnomAD3 exomes AF: 0.0449 AC: 10223 AN: 227888 Hom.: 558 AF XY: 0.0400 AC XY: 4928 AN XY: 123202

Gnomad AFR exome AF: 0.240

Gnomad AMR exome AF: 0.0292

Gnomad ASJ exome AF: 0.0232

Gnomad EAS exome AF: 0.0000596

Gnomad SAS exome AF: 0.00621

Gnomad FIN exome AF: 0.0725

Gnomad NFE exome AF: 0.0377

Gnomad OTH exome AF: 0.0375

GnomAD4 exome AF: 0.0387 AC: 55964 AN: 1446748 Hom.: 2083 Cov.: 31 AF XY: 0.0373 AC XY: 26835 AN XY: 718796

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.0313

Gnomad4 ASJ exome AF: 0.0246

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.00726

Gnomad4 FIN exome AF: 0.0671

Gnomad4 NFE exome AF: 0.0349

Gnomad4 OTH exome AF: 0.0432

GnomAD4 genome AF: 0.0972 AC: 14766 AN: 151964 Hom.: 1408 Cov.: 32 AF XY: 0.0972 AC XY: 7219 AN XY: 74282

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.0508

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00873

Gnomad4 FIN AF: 0.0784

Gnomad4 NFE AF: 0.0397

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0670 Hom.: 145

Bravo AF: 0.102

Asia WGS AF: 0.0140 AC: 50 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 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.077
Dann	Benign	0.51

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: rs60896170; hg19: chr4-5624223;