rs80359844
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001017420.3(ESCO2):c.252_253del(p.Ser85PhefsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. V84V) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001017420.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESCO2 | NM_001017420.3 | c.252_253del | p.Ser85PhefsTer6 | frameshift_variant | 3/11 | ENST00000305188.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESCO2 | ENST00000305188.13 | c.252_253del | p.Ser85PhefsTer6 | frameshift_variant | 3/11 | 1 | NM_001017420.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250588Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135530
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461818Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727208
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2023 | ClinVar contains an entry for this variant (Variation ID: 21241). This sequence change creates a premature translational stop signal (p.Ser85Phefs*6) in the ESCO2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ESCO2 are known to be pathogenic (PMID: 15821733, 16380922). This variant is present in population databases (rs756508716, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Roberts syndrome (PMID: 15821733). This variant is also known as p.Val84fsX7. For these reasons, this variant has been classified as Pathogenic. - |
Roberts-SC phocomelia syndrome Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at