rs80359851
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001017420.3(ESCO2):c.745_746del(p.Val249GlnfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,608,366 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
ESCO2
NM_001017420.3 frameshift
NM_001017420.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0380
Genes affected
ESCO2 (HGNC:27230): (establishment of sister chromatid cohesion N-acetyltransferase 2) This gene encodes a protein that may have acetyltransferase activity and may be required for the establishment of sister chromatid cohesion during the S phase of mitosis. Mutations in this gene have been associated with Roberts syndrome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
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Very rare variant in population databases, with high coverage;
PP5
?
Variant 8-27777051-CTG-C is Pathogenic according to our data. Variant chr8-27777051-CTG-C is described in ClinVar as [Pathogenic]. Clinvar id is 21246.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-27777051-CTG-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESCO2 | NM_001017420.3 | c.745_746del | p.Val249GlnfsTer2 | frameshift_variant | 3/11 | ENST00000305188.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESCO2 | ENST00000305188.13 | c.745_746del | p.Val249GlnfsTer2 | frameshift_variant | 3/11 | 1 | NM_001017420.3 | P1 | |
ESCO2 | ENST00000524293.1 | n.763_764del | non_coding_transcript_exon_variant | 2/2 | 1 | ||||
ESCO2 | ENST00000522378.5 | c.745_746del | p.Val249GlnfsTer2 | frameshift_variant, NMD_transcript_variant | 3/12 | 1 | |||
ESCO2 | ENST00000523910.1 | n.544_545del | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152048Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1456318Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 724088
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2023 | For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Val249Glnfs*2) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ESCO2-related conditions (PMID: 16775838). ClinVar contains an entry for this variant (Variation ID: 21246). - |
Roberts-SC phocomelia syndrome Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at