rs58869180

Variant names:

• chr4-5628754-A-C
• rs58869180
• NM_147127.5:c.1711-20T>G

Your query was ambiguous. Multiple possible variants found:

• chr4-5628754-A-C
• chr4-5628754-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_147127.5(EVC2):​c.1711-20T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,484,598 control chromosomes in the GnomAD database, including 2,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (1166 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (1036 hom.)
• Consequence: EVC2 NM_147127.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.87
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• acrofacial dysostosis, Weyers type

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• Ellis-van Creveld syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Myriad Women's Health, Laboratory for Molecular Medicine

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-5628754-A-C is Benign according to our data. Variant chr4-5628754-A-C is described in ClinVar as Benign. ClinVar VariationId is 262606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_147127.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC2	NM_147127.5	MANE Select	c.1711-20T>G		intron	N/A	NP_667338.3
	EVC2	NM_001166136.2		c.1471-20T>G		intron	N/A	NP_001159608.1	Q86UK5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVC2	ENST00000344408.10	TSL:1 MANE Select	c.1711-20T>G		intron	N/A	ENSP00000342144.5	Q86UK5-1
	EVC2	ENST00000310917.6	TSL:1	c.1471-20T>G		intron	N/A	ENSP00000311683.2	Q86UK5-2
	EVC2	ENST00000475313.5	TSL:1	n.1471-20T>G		intron	N/A	ENSP00000431981.1	A0A0C4DGE7

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10353 AN: 150786 Hom.: 1163 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00168

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.0479

GnomAD2 exomes AF: 0.0186 AC: 4607 AN: 247834 AF XY: 0.0139

Gnomad AFR exome AF: 0.239

Gnomad AMR exome AF: 0.0150

Gnomad ASJ exome AF: 0.00499

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00144

Gnomad OTH exome AF: 0.0142

GnomAD4 exome AF: 0.00848 AC: 11315 AN: 1333696 Hom.: 1036 Cov.: 30 AF XY: 0.00742 AC XY: 4958 AN XY: 668028

African (AFR) AF: 0.250 AC: 7956 AN: 31794

American (AMR) AF: 0.0171 AC: 746 AN: 43746

Ashkenazi Jewish (ASJ) AF: 0.00486 AC: 123 AN: 25308

East Asian (EAS) AF: 0.00 AC: 0 AN: 37972

South Asian (SAS) AF: 0.000908 AC: 75 AN: 82626

European-Finnish (FIN) AF: 0.0000585 AC: 3 AN: 51272

Middle Eastern (MID) AF: 0.0314 AC: 167 AN: 5322

European-Non Finnish (NFE) AF: 0.00114 AC: 1137 AN: 999842

Other (OTH) AF: 0.0199 AC: 1108 AN: 55814

GnomAD4 genome AF: 0.0688 AC: 10383 AN: 150902 Hom.: 1166 Cov.: 32 AF XY: 0.0666 AC XY: 4912 AN XY: 73710

African (AFR) AF: 0.234 AC: 9623 AN: 41060

American (AMR) AF: 0.0335 AC: 505 AN: 15096

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5098

South Asian (SAS) AF: 0.00126 AC: 6 AN: 4752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10414

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00143 AC: 97 AN: 67726

Other (OTH) AF: 0.0474 AC: 99 AN: 2090

Alfa AF: 0.0376 Hom.: 96

Bravo AF: 0.0796

Asia WGS AF: 0.0210 AC: 73 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.022
DANN	Benign	0.53
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs58869180;

hg19: chr4-5630481;