rs557813179

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The ENST00000305188.13(ESCO2):​c.383G>A​(p.Gly128Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,618 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G128R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000037 ( 1 hom. )

Consequence

ESCO2
ENST00000305188.13 missense

Scores

19

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -0.00700
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.019416422).
BP6
Variant 8-27776691-G-A is Benign according to our data. Variant chr8-27776691-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 158574.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ESCO2NM_001017420.3 linkuse as main transcriptc.383G>A p.Gly128Glu missense_variant 3/11 ENST00000305188.13 NP_001017420.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ESCO2ENST00000305188.13 linkuse as main transcriptc.383G>A p.Gly128Glu missense_variant 3/111 NM_001017420.3 ENSP00000306999 P1Q56NI9-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152028
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000996
AC:
25
AN:
250878
Hom.:
1
AF XY:
0.000111
AC XY:
15
AN XY:
135648
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000817
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000369
AC:
54
AN:
1461472
Hom.:
1
Cov.:
31
AF XY:
0.0000468
AC XY:
34
AN XY:
727034
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000591
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152146
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000936
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.000115
AC:
14
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 07, 2021The c.383G>A (p.G128E) alteration is located in exon 3 (coding exon 2) of the ESCO2 gene. This alteration results from a G to A substitution at nucleotide position 383, causing the glycine (G) at amino acid position 128 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Roberts-SC phocomelia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoFeb 08, 2013- -
Roberts syndrome Benign:1
Benign, no assertion criteria providedclinical testingNatera, Inc.Oct 28, 2019- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 25, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
4.6
DANN
Benign
0.48
DEOGEN2
Benign
0.022
T;T;.
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.076
N
LIST_S2
Benign
0.60
T;T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.019
T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.85
.;L;.
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.63
N;N;N
REVEL
Benign
0.098
Sift
Benign
0.35
T;T;T
Sift4G
Benign
0.58
T;T;T
Polyphen
0.0050
.;B;.
Vest4
0.12
MutPred
0.11
Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);Gain of solvent accessibility (P = 0.0456);
MVP
0.40
MPC
0.16
ClinPred
0.029
T
GERP RS
-0.0062
Varity_R
0.028
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs557813179; hg19: chr8-27634208; COSMIC: COSV59414946; COSMIC: COSV59414946; API