rs141631911

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001017420.3(ESCO2):c.764T>C(p.Phe255Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,605,628 control chromosomes in the GnomAD database, including 79 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F255L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0026 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 71 hom. )

Consequence

ESCO2
NM_001017420.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.333

Publications

6 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=0.0027889013).

BP6

Variant 8-27777072-T-C is Benign according to our data. Variant chr8-27777072-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 196300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00262 (399/152270) while in subpopulation AMR AF = 0.0182 (279/15300). AF 95% confidence interval is 0.0165. There are 8 homozygotes in GnomAd4. There are 197 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017420.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESCO2	NM_001017420.3	MANE Select	c.764T>C	p.Phe255Ser	missense	Exon 3 of 11	NP_001017420.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ESCO2	ENST00000305188.13	TSL:1 MANE Select	c.764T>C	p.Phe255Ser	missense	Exon 3 of 11	ENSP00000306999.8
ESCO2	ENST00000522378.5	TSL:1	n.764T>C		non_coding_transcript_exon	Exon 3 of 12	ENSP00000428928.1
ESCO2	ENST00000524293.1	TSL:1	n.782T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

400

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00803

AC:

1943

AN:

242026

AF XY:

0.00627

show subpopulations

Gnomad AFR exome

AF:

0.00119

Gnomad AMR exome

AF:

0.0556

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000113

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000495

Gnomad OTH exome

AF:

0.00683

GnomAD4 exome

AF:

0.00192

AC:

2796

AN:

1453358

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1224

AN XY:

722530

show subpopulations

African (AFR)

AF:

0.000641

AC:

AN:

32744

American (AMR)

AF:

0.0477

AC:

2027

AN:

42470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25804

East Asian (EAS)

AF:

0.000227

AC:

AN:

39666

South Asian (SAS)

AF:

0.00110

AC:

AN:

83520

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00926

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.000438

AC:

486

AN:

1110134

Other (OTH)

AF:

0.00178

AC:

107

AN:

59980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

146

292

438

584

730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.00262

AC:

399

AN:

152270

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

197

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

41556

American (AMR)

AF:

0.0182

AC:

279

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000618

AC:

AN:

68010

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00119

Hom.:

Bravo

AF:

0.00578

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00664

AC:

806

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jun 05, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jan 25, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nov 08, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Roberts-SC phocomelia syndrome

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not specified

Benign:1

Mar 17, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.9

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.026

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

-0.33

PrimateAI

Benign

0.33

PROVEAN

Benign

0.020

REVEL

Benign

0.018

Sift

Benign

0.44

Sift4G

Benign

0.42

Polyphen

0.0010

Vest4

0.10

MVP

0.44

MPC

0.21

ClinPred

0.000031

GERP RS

0.25

Varity_R

0.038

gMVP

0.20

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over