8-27774626-C-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.-17+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 152,170 control chromosomes in the GnomAD database, including 13,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 13604 hom., cov: 32)

Exomes 𝑓: 0.43 ( 23 hom. )

Consequence

ESCO2
NM_001017420.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.25

Publications

7 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 (BayesDel_noAF=-0.81).

BP6

Variant 8-27774626-C-T is Benign according to our data. Variant chr8-27774626-C-T is described in ClinVar as [Benign]. Clinvar id is 516218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESCO2	NM_001017420.3 link	c.-17+19C>T		intron_variant	Intron 1 of 10	ENST00000305188.13	NP_001017420.1	Q56NI9-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ESCO2	ENST00000305188.13 link	c.-17+19C>T	intron_variant	Intron 1 of 10	1	NM_001017420.3	ENSP00000306999.8	Q56NI9-1
ESCO2	ENST00000522378.5 link	n.-17+19C>T	intron_variant	Intron 1 of 11	1		ENSP00000428928.1	E5RFE4
ESCO2	ENST00000523566.5 link	c.-16-873C>T	intron_variant	Intron 1 of 2	3		ENSP00000428435.1	E5RIE3
ESCO2	ENST00000519637.1 link	c.-218C>T	upstream_gene_variant		3		ENSP00000428027.1	E5RFP7

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63439

AN:

151834

Hom.:

13580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.269

Gnomad EAS

AF:

0.615

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.401

GnomAD4 exome

AF:

0.426

AC:

AN:

216

Hom.:

Cov.:

AF XY:

0.407

AC XY:

AN XY:

162

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.333

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.667

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.421

AC:

AN:

178

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.529

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.418

AC:

63521

AN:

151954

Hom.:

13604

Cov.:

AF XY:

0.417

AC XY:

31009

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.377

AC:

15631

AN:

41430

American (AMR)

AF:

0.492

AC:

7520

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.269

AC:

932

AN:

3468

East Asian (EAS)

AF:

0.615

AC:

3176

AN:

5162

South Asian (SAS)

AF:

0.432

AC:

2080

AN:

4812

European-Finnish (FIN)

AF:

0.371

AC:

3910

AN:

10542

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.425

AC:

28845

AN:

67948

Other (OTH)

AF:

0.405

AC:

854

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1917

3834

5751

7668

9585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.311

Hom.:

886

Bravo

AF:

0.429

Asia WGS

AF:

0.546

AC:

1894

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 04, 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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

(source)

DANN

Benign

0.87

PhyloP100

-2.3

PromoterAI

-0.22

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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8-27774626-C-T

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