rs4689261

Positions:

• chr4-5575608-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000344408.10(EVC2):​c.3272+632C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,078 control chromosomes in the GnomAD database, including 18,657 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 0.47 (18657 hom., cov: 33)
• Consequence: EVC2 ENST00000344408.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVC2	NM_147127.5	c.3272+632C>T		intron_variant		ENST00000344408.10	NP_667338.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVC2	ENST00000344408.10	c.3272+632C>T		intron_variant		1	NM_147127.5	ENSP00000342144	P2
EVC2	ENST00000310917.6	c.3032+632C>T		intron_variant		1		ENSP00000311683	A2
EVC2	ENST00000475313.5	c.3032+632C>T		intron_variant, NMD_transcript_variant		1		ENSP00000431981
EVC2	ENST00000509670.1	c.*1665+632C>T		intron_variant, NMD_transcript_variant		1		ENSP00000423876

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71471 AN: 151958 Hom.: 18592 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.858

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.471 AC: 71595 AN: 152078 Hom.: 18657 Cov.: 33 AF XY: 0.480 AC XY: 35681 AN XY: 74334

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.858

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.454

Alfa AF: 0.447 Hom.: 2343

Bravo AF: 0.483

Asia WGS AF: 0.723 AC: 2512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.29
DANN	Benign	0.75

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: rs4689261; hg19: chr4-5577335;