Genetic Variant ESCO2:c.-16-149T>G (chr8-27775350-T-G) – ACMG Classification: Benign (-20 pts)

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.-16-149T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 702,244 control chromosomes in the GnomAD database, including 265,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.86 ( 56591 hom., cov: 32)

Exomes 𝑓: 0.87 ( 208777 hom. )

Consequence

ESCO2
NM_001017420.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.826

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 8-27775350-T-G is Benign according to our data. Variant chr8-27775350-T-G is described in ClinVar as [Benign]. Clinvar id is 1254162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESCO2	NM_001017420.3 link	c.-16-149T>G		intron_variant	Intron 1 of 10	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.-16-149T>G		intron_variant	Intron 1 of 10	1	NM_001017420.3	ENSP00000306999.8		Q56NI9-1

Frequencies

GnomAD3 genomes

AF:

0.861

AC:

130924

AN:

152054

Hom.:

56531

Cov.:

show subpopulations

Gnomad AFR

AF:

0.827

Gnomad AMI

AF:

0.802

Gnomad AMR

AF:

0.916

Gnomad ASJ

AF:

0.868

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.848

Gnomad FIN

AF:

0.840

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.863

Gnomad OTH

AF:

0.876

GnomAD4 exome

AF:

0.870

AC:

478493

AN:

550072

Hom.:

208777

AF XY:

0.867

AC XY:

255656

AN XY:

294834

show subpopulations

African (AFR)

AF:

0.824

AC:

12546

AN:

15232

American (AMR)

AF:

0.938

AC:

28970

AN:

30880

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

14931

AN:

17296

East Asian (EAS)

AF:

1.00

AC:

32678

AN:

32694

South Asian (SAS)

AF:

0.836

AC:

47872

AN:

57286

European-Finnish (FIN)

AF:

0.846

AC:

39698

AN:

46936

Middle Eastern (MID)

AF:

0.852

AC:

1999

AN:

2346

European-Non Finnish (NFE)

AF:

0.862

AC:

274024

AN:

317982

Other (OTH)

AF:

0.876

AC:

25775

AN:

29420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

3010

6020

9030

12040

15050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.861

AC:

131044

AN:

152172

Hom.:

56591

Cov.:

AF XY:

0.862

AC XY:

64146

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.827

AC:

34317

AN:

41492

American (AMR)

AF:

0.917

AC:

14020

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.868

AC:

3011

AN:

3470

East Asian (EAS)

AF:

0.999

AC:

5186

AN:

5190

South Asian (SAS)

AF:

0.848

AC:

4085

AN:

4816

European-Finnish (FIN)

AF:

0.840

AC:

8886

AN:

10574

Middle Eastern (MID)

AF:

0.874

AC:

257

AN:

294

European-Non Finnish (NFE)

AF:

0.863

AC:

58696

AN:

68018

Other (OTH)

AF:

0.879

AC:

1855

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

924

1847

2771

3694

4618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.855

Hom.:

8225

Bravo

AF:

0.868

Asia WGS

AF:

0.943

AC:

3281

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 07, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.4

(source)

DANN

Benign

0.34

PhyloP100

-0.83

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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chr8-27775350-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over