chr8-27776813-C-T
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001017420.3(ESCO2):c.505C>T(p.Arg169*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001017420.3 stop_gained
Scores
Clinical Significance
Conservation
Publications
- Roberts-SC phocomelia syndromeInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
- Roberts syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
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ACMG classification
Our verdict: Pathogenic. The variant received 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD2 exomes AF: 0.00000796 AC: 2AN: 251250 AF XY: 0.00000736 show subpopulations
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461802Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727212 show subpopulations
Age Distribution
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Roberts-SC phocomelia syndrome Pathogenic:2Other:1
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not provided Pathogenic:1
This sequence change creates a premature translational stop signal (p.Arg169*) 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 (rs80359849, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with Roberts syndrome (PMID: 15821733). ClinVar contains an entry for this variant (Variation ID: 1736). For these reasons, this variant has been classified as Pathogenic. -
Roberts-SC phocomelia syndrome;C0796099:Juberg-Hayward syndrome Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at