chr4-5562881-G-GGCATTCAAAAAGTTCTTCTTTTTC
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5
The NM_147127.5(EVC2):c.3893_3894insGAAAAAGAAGAACTTTTTGAATGC(p.Lys1293_Lys1300dup) variant causes a inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
EVC2
NM_147127.5 inframe_insertion
NM_147127.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.03
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_147127.5.
PP5
?
Variant 4-5562881-G-GGCATTCAAAAAGTTCTTCTTTTTC is Pathogenic according to our data. Variant chr4-5562881-G-GGCATTCAAAAAGTTCTTCTTTTTC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 183329.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EVC2 | NM_147127.5 | c.3893_3894insGAAAAAGAAGAACTTTTTGAATGC | p.Lys1293_Lys1300dup | inframe_insertion | 22/22 | ENST00000344408.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EVC2 | ENST00000344408.10 | c.3893_3894insGAAAAAGAAGAACTTTTTGAATGC | p.Lys1293_Lys1300dup | inframe_insertion | 22/22 | 1 | NM_147127.5 | P2 | |
EVC2 | ENST00000310917.6 | c.3653_3654insGAAAAAGAAGAACTTTTTGAATGC | p.Lys1213_Lys1220dup | inframe_insertion | 22/22 | 1 | A2 | ||
EVC2 | ENST00000475313.5 | c.3419+2376_3419+2377insGAAAAAGAAGAACTTTTTGAATGC | intron_variant, NMD_transcript_variant | 1 | |||||
EVC2 | ENST00000509670.1 | c.*2286_*2287insGAAAAAGAAGAACTTTTTGAATGC | 3_prime_UTR_variant, NMD_transcript_variant | 23/23 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Meckel-Gruber syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre | Dec 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at