4-5685370-CCG-TCC

Variant names:

• chr4-5685370-CCG-TCC
• NM_147127.5:c.814_816delCGGinsGGA
• EVC2 p.Arg272Gly

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_147127.5(EVC2):​c.814_816delCGGinsGGA​(p.Arg272Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R272W) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EVC2 NM_147127.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14
• 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: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• Ellis-van Creveld syndrome

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.814_816delCGGinsGGA	p.Arg272Gly	missense splice_region	N/A	NP_667338.3
	EVC2	NM_001166136.2		c.574_576delCGGinsGGA	p.Arg192Gly	missense splice_region	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.814_816delCGGinsGGA	p.Arg272Gly	missense splice_region	N/A	ENSP00000342144.5	Q86UK5-1
	EVC2	ENST00000310917.6	TSL:1	c.574_576delCGGinsGGA	p.Arg192Gly	missense splice_region	N/A	ENSP00000311683.2	Q86UK5-2
	EVC2	ENST00000475313.5	TSL:1	n.574_576delCGGinsGGA		splice_region non_coding_transcript_exon	Exon 6 of 23	ENSP00000431981.1	A0A0C4DGE7

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

Splicing

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

hg19: chr4-5687097;