chr4-5562893-GTTC-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_147127.5(EVC2):c.3879_3881del(p.Lys1293del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000052 in 1,614,178 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.00024 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
EVC2
NM_147127.5 inframe_deletion
NM_147127.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.94
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_147127.5. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EVC2 | NM_147127.5 | c.3879_3881del | p.Lys1293del | inframe_deletion | 22/22 | ENST00000344408.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC2 | ENST00000344408.10 | c.3879_3881del | p.Lys1293del | inframe_deletion | 22/22 | 1 | NM_147127.5 | P2 | |
EVC2 | ENST00000310917.6 | c.3639_3641del | p.Lys1213del | inframe_deletion | 22/22 | 1 | A2 | ||
EVC2 | ENST00000475313.5 | c.3419+2362_3419+2364del | intron_variant, NMD_transcript_variant | 1 | |||||
EVC2 | ENST00000509670.1 | c.*2272_*2274del | 3_prime_UTR_variant, NMD_transcript_variant | 23/23 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152208Hom.: 1 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
36
AN:
152208
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000119 AC: 30AN: 251448Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135894
GnomAD3 exomes
AF:
AC:
30
AN:
251448
Hom.:
AF XY:
AC XY:
16
AN XY:
135894
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461852Hom.: 0 AF XY: 0.0000358 AC XY: 26AN XY: 727230
GnomAD4 exome
AF:
AC:
48
AN:
1461852
Hom.:
AF XY:
AC XY:
26
AN XY:
727230
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000236 AC: 36AN: 152326Hom.: 1 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74480
GnomAD4 genome
?
AF:
AC:
36
AN:
152326
Hom.:
Cov.:
32
AF XY:
AC XY:
22
AN XY:
74480
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Ellis-van Creveld syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Feb 03, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | May 24, 2023 | The EVC2 c.3879_3881del; p.Lys1293del variant (rs752839237), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 550613). This variant is found in the Latino/Admixed American population with an allele frequency of 0.07% (25/35434 alleles) in the Genome Aggregation Database. This variant deletes a single lysine residue leaving the rest of the protein in-frame. Due to limited information, the clinical significance of this variant is uncertain at this time. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at