rs10025164

Variant names:

• chr4-5615568-T-C
• rs10025164
• NM_147127.5:c.2707-24A>G

Your query was ambiguous. Multiple possible variants found:

• chr4-5615568-T-C
• chr4-5615568-T-G

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.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:3
• Conservation: PhyloP100: -2.08
• Publications: 8 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 4-5615568-T-C is Benign according to our data. Variant chr4-5615568-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

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.2707-24A>G		intron	N/A	NP_667338.3
	EVC2	NM_001166136.2		c.2467-24A>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.2707-24A>G		intron	N/A	ENSP00000342144.5	Q86UK5-1
	EVC2	ENST00000310917.6	TSL:1	c.2467-24A>G		intron	N/A	ENSP00000311683.2	Q86UK5-2
	EVC2	ENST00000475313.5	TSL:1	n.2467-24A>G		intron	N/A	ENSP00000431981.1	A0A0C4DGE7

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

GnomAD2 exomes AF: 0.344 AC: 86576 AN: 251354 AF XY: 0.334

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 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

African (AFR) AF: 0.542 AC: 18154 AN: 33466

American (AMR) AF: 0.400 AC: 17897 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 6707 AN: 26132

East Asian (EAS) AF: 0.598 AC: 23744 AN: 39686

South Asian (SAS) AF: 0.280 AC: 24176 AN: 86248

European-Finnish (FIN) AF: 0.337 AC: 17998 AN: 53392

Middle Eastern (MID) AF: 0.306 AC: 1766 AN: 5766

European-Non Finnish (NFE) AF: 0.273 AC: 303011 AN: 1111794

Other (OTH) AF: 0.310 AC: 18718 AN: 60382

GnomAD4 genome AF: 0.371 AC: 56455 AN: 152004 Hom.: 11609 Cov.: 32 AF XY: 0.376 AC XY: 27978 AN XY: 74312

African (AFR) AF: 0.533 AC: 22074 AN: 41448

American (AMR) AF: 0.374 AC: 5726 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 886 AN: 3472

East Asian (EAS) AF: 0.603 AC: 3106 AN: 5148

South Asian (SAS) AF: 0.292 AC: 1406 AN: 4808

European-Finnish (FIN) AF: 0.348 AC: 3677 AN: 10570

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18569 AN: 67950

Other (OTH) AF: 0.330 AC: 697 AN: 2112

Alfa AF: 0.319 Hom.: 2777

Bravo AF: 0.387

Asia WGS AF: 0.451 AC: 1567 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.066
DANN	Benign	0.34
PhyloP100		-2.1
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: rs10025164;

hg19: chr4-5617295;

COSMIC: COSV107399039;