chr4-5637692-G-A

Variant names:

• chr4-5637692-G-A
• rs12648800
• NM_147127.5:c.1470+2822C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_147127.5(EVC2):​c.1470+2822C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,070 control chromosomes in the GnomAD database, including 4,502 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4502 hom., cov: 32)
• Consequence: EVC2 NM_147127.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.484
• Publications: 1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• Ellis-van Creveld syndrome

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVC2	NM_147127.5	c.1470+2822C>T		intron_variant	Intron 10 of 21	ENST00000344408.10	NP_667338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVC2	ENST00000344408.10	c.1470+2822C>T		intron_variant	Intron 10 of 21	1	NM_147127.5	ENSP00000342144.5
EVC2	ENST00000310917.6	c.1230+2822C>T		intron_variant	Intron 10 of 21	1		ENSP00000311683.2
EVC2	ENST00000475313.5	n.1230+2822C>T		intron_variant	Intron 10 of 22	1		ENSP00000431981.1
EVC2	ENST00000509670.1	n.1222+2830C>T		intron_variant	Intron 11 of 22	1		ENSP00000423876.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32942 AN: 151952 Hom.: 4495 Cov.: 32

Gnomad AFR AF: 0.0860

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.217 AC: 32957 AN: 152070 Hom.: 4502 Cov.: 32 AF XY: 0.225 AC XY: 16704 AN XY: 74328

African (AFR) AF: 0.0860 AC: 3567 AN: 41500

American (AMR) AF: 0.329 AC: 5031 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3470

East Asian (EAS) AF: 0.606 AC: 3128 AN: 5160

South Asian (SAS) AF: 0.282 AC: 1358 AN: 4812

European-Finnish (FIN) AF: 0.279 AC: 2942 AN: 10546

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15378 AN: 67994

Other (OTH) AF: 0.217 AC: 457 AN: 2108

Alfa AF: 0.105 Hom.: 171

Bravo AF: 0.221

Asia WGS AF: 0.398 AC: 1384 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.40
PhyloP100		-0.48
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

Other links and lift over

dbSNP: rs12648800; hg19: chr4-5639419;