rs80359849

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001017420.3(ESCO2):​c.505C>G​(p.Arg169Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ESCO2
NM_001017420.3 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.299

Publications

0 publications found
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]
ESCO2 Gene-Disease associations (from GenCC):
  • Roberts-SC phocomelia syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
  • Roberts syndrome
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18253773).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ESCO2NM_001017420.3 linkc.505C>G p.Arg169Gly missense_variant Exon 3 of 11 ENST00000305188.13 NP_001017420.1 Q56NI9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ESCO2ENST00000305188.13 linkc.505C>G p.Arg169Gly missense_variant Exon 3 of 11 1 NM_001017420.3 ENSP00000306999.8 Q56NI9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461802
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727212
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39694
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53354
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1112002
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.043
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
11
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T;T
Eigen
Benign
-0.017
Eigen_PC
Benign
-0.065
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.76
T;T
M_CAP
Benign
0.062
D
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Uncertain
2.4
.;M
PhyloP100
0.30
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-3.5
D;N
REVEL
Benign
0.12
Sift
Benign
0.10
T;T
Sift4G
Uncertain
0.016
D;T
Polyphen
0.83
.;P
Vest4
0.22
MutPred
0.23
Loss of MoRF binding (P = 0.0268);Loss of MoRF binding (P = 0.0268);
MVP
0.76
MPC
0.24
ClinPred
0.74
D
GERP RS
2.9
Varity_R
0.078
gMVP
0.38
Mutation Taster
=99/1
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs80359849; hg19: chr8-27634330; API