rs4732748

Positions:

chr8-27776547-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000305188.13(ESCO2):c.239C>T(p.Ala80Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,613,932 control chromosomes in the GnomAD database, including 9,316 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A80A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.10 ( 942 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8374 hom. )

Consequence

ESCO2
ENST00000305188.13 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: 0.0330

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018123686).

BP6

Variant 8-27776547-C-T is Benign according to our data. Variant chr8-27776547-C-T is described in ClinVar as [Benign]. Clinvar id is 21240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESCO2	NM_001017420.3 linkuse as main transcript	c.239C>T	p.Ala80Val	missense_variant	3/11	ENST00000305188.13	NP_001017420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESCO2	ENST00000305188.13 linkuse as main transcript	c.239C>T	p.Ala80Val	missense_variant	3/11	1	NM_001017420.3	ENSP00000306999	P1	Q56NI9-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15983

AN:

152088

Hom.:

944

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0954

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.0819

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0969

Gnomad OTH

AF:

0.125

GnomAD3 exomes

AF:

0.115

AC:

28663

AN:

250260

Hom.:

1996

AF XY:

0.118

AC XY:

15955

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.0953

Gnomad AMR exome

AF:

0.0792

Gnomad ASJ exome

AF:

0.182

Gnomad EAS exome

AF:

0.244

Gnomad SAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.0865

Gnomad NFE exome

AF:

0.0958

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.101

AC:

148296

AN:

1461726

Hom.:

8374

Cov.:

AF XY:

0.104

AC XY:

75262

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.0955

Gnomad4 AMR exome

AF:

0.0811

Gnomad4 ASJ exome

AF:

0.177

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.0864

Gnomad4 NFE exome

AF:

0.0919

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.105

AC:

15972

AN:

152206

Hom.:

942

Cov.:

AF XY:

0.105

AC XY:

7814

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0953

Gnomad4 AMR

AF:

0.108

Gnomad4 ASJ

AF:

0.174

Gnomad4 EAS

AF:

0.239

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.0819

Gnomad4 NFE

AF:

0.0969

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.104

Hom.:

2218

Bravo

AF:

0.105

TwinsUK

AF:

0.0917

AC:

340

ALSPAC

AF:

0.0898

AC:

346

ESP6500AA

AF:

0.0976

AC:

430

ESP6500EA

AF:

0.0993

AC:

854

ExAC

AF:

0.115

AC:

13903

Asia WGS

AF:

0.181

AC:

627

AN:

3476

EpiCase

AF:

0.105

EpiControl

AF:

0.107

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Roberts-SC phocomelia syndrome

Benign:3Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 08, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 14, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Juberg-Hayward syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.46

CADD

Benign

3.4

DANN

Benign

0.88

DEOGEN2

Benign

0.039

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.55

T;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

.;M;.

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.051

Sift

Benign

0.49

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0040

.;B;.

Vest4

0.025

MPC

0.12

ClinPred

0.00062

GERP RS

1.8

Varity_R

0.032

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over