8-27777072-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001017420.3(ESCO2):​c.764T>G​(p.Phe255Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

ESCO2
NM_001017420.3 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.333
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16239664).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ESCO2NM_001017420.3 linkc.764T>G p.Phe255Cys 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.764T>G p.Phe255Cys missense_variant Exon 3 of 11 1 NM_001017420.3 ENSP00000306999.8 Q56NI9-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1453368
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
722534
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
3.1
DANN
Benign
0.94
DEOGEN2
Benign
0.084
T
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.045
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.80
N
REVEL
Benign
0.12
Sift
Benign
0.18
T
Sift4G
Benign
0.18
T
Polyphen
0.76
P
Vest4
0.38
MutPred
0.13
Loss of catalytic residue at F255 (P = 0.0681);
MVP
0.65
MPC
0.18
ClinPred
0.24
T
GERP RS
0.25
Varity_R
0.056
gMVP
0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-27634589; API