NM_001017420.3:c.239C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001017420.3(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. 16/21 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
NM_001017420.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0330

Publications

30 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

ESCO2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ESCO2	NM_001017420.3 link	c.239C>T	p.Ala80Val	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
ESCO2	ENST00000305188.13 link	c.239C>T	p.Ala80Val	missense_variant	Exon 3 of 11	1	NM_001017420.3	ENSP00000306999.8		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

GnomAD2 exomes

AF:

0.115

AC:

28663

AN:

250260

AF XY:

0.118

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 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

African (AFR)

AF:

0.0955

AC:

3196

AN:

33478

American (AMR)

AF:

0.0811

AC:

3628

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

4637

AN:

26130

East Asian (EAS)

AF:

0.214

AC:

8477

AN:

39680

South Asian (SAS)

AF:

0.156

AC:

13435

AN:

86242

European-Finnish (FIN)

AF:

0.0864

AC:

4614

AN:

53396

Middle Eastern (MID)

AF:

0.161

AC:

928

AN:

5768

European-Non Finnish (NFE)

AF:

0.0919

AC:

102174

AN:

1111926

Other (OTH)

AF:

0.119

AC:

7207

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

7675

15349

23024

30698

38373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3900

7800

11700

15600

19500

<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

AF:

0.105

AC:

15972

AN:

152206

Hom.:

942

Cov.:

AF XY:

0.105

AC XY:

7814

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0953

AC:

3955

AN:

41520

American (AMR)

AF:

0.108

AC:

1652

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

603

AN:

3470

East Asian (EAS)

AF:

0.239

AC:

1237

AN:

5182

South Asian (SAS)

AF:

0.154

AC:

741

AN:

4822

European-Finnish (FIN)

AF:

0.0819

AC:

868

AN:

10598

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0969

AC:

6594

AN:

68016

Other (OTH)

AF:

0.124

AC:

262

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

739

1477

2216

2954

3693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.104

Hom.:

3048

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

GeneReviews

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 14, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Feb 08, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Juberg-Hayward syndrome

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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;.

PhyloP100

0.033

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over