chr8-27775540-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001017420.3(ESCO2):c.26G>A(p.Arg9Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R9R) has been classified as Likely benign.
Frequency
Consequence
NM_001017420.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ESCO2 | NM_001017420.3 | c.26G>A | p.Arg9Lys | missense_variant | 2/11 | ENST00000305188.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ESCO2 | ENST00000305188.13 | c.26G>A | p.Arg9Lys | missense_variant | 2/11 | 1 | NM_001017420.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251446Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461816Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727204
GnomAD4 genome ? AF: 0.0000853 AC: 13AN: 152336Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74496
ClinVar
Submissions by phenotype
ESCO2-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 26, 2023 | The ESCO2 c.26G>A variant is predicted to result in the amino acid substitution p.Arg9Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.024% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-27633057-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2023 | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 9 of the ESCO2 protein (p.Arg9Lys). This variant is present in population databases (rs145248677, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ESCO2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at