rs755381180
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PM4_SupportingPP5_Very_Strong
The NM_153717.3(EVC):c.904_906delAAG(p.Lys302del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.0000118 in 1,613,952 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_153717.3 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EVC | ENST00000264956.11 | c.904_906delAAG | p.Lys302del | conservative_inframe_deletion | Exon 7 of 21 | 1 | NM_153717.3 | ENSP00000264956.6 | ||
EVC | ENST00000509451.1 | c.904_906delAAG | p.Lys302del | conservative_inframe_deletion | Exon 7 of 12 | 1 | ENSP00000426774.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251470Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135908
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461780Hom.: 0 AF XY: 0.0000110 AC XY: 8AN XY: 727214
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74338
ClinVar
Submissions by phenotype
Ellis-van Creveld syndrome;C0457013:Curry-Hall syndrome Pathogenic:2
In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 446661). This variant has been observed in individual(s) with Ellis-van Creveld syndrome (PMID: 10700184, 23220543, 29068549; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs755381180, gnomAD 0.005%). This variant, c.904_906del, results in the deletion of 1 amino acid(s) of the EVC protein (p.Lys302del), but otherwise preserves the integrity of the reading frame. -
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Short-rib thoracic dysplasia 6 with or without polydactyly Pathogenic:2
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Ellis-van Creveld syndrome Pathogenic:1
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not provided Pathogenic:1
Not observed at a significant frequency in large population cohorts (gnomAD); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 23220543, 18947413, 16404586, 29068549, 17024374, 19810119, 10700184) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at