Variant 8-27774626-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 (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. Variant chr8-27774626-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
ESCO2	NM_001017420.3 link	c.-17+19C>T		intron_variant		ENST00000305188.13	NP_001017420.1	Q56NI9-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ESCO2	ENST00000305188.13 link	c.-17+19C>T	intron_variant	1	NM_001017420.3	ENSP00000306999.8	Q56NI9-1
ESCO2	ENST00000522378.5 link	n.-17+19C>T	intron_variant	1		ENSP00000428928.1	E5RFE4
ESCO2	ENST00000523566.5 link	c.-16-873C>T	intron_variant	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

Gnomad4 AFR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.333

Gnomad4 FIN exome

AF:

0.667

Gnomad4 NFE exome

AF:

0.421

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.418

AC:

63521

AN:

151954

Hom.:

13604

Cov.:

AF XY:

0.417

AC XY:

31009

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.377

Gnomad4 AMR

AF:

0.492

Gnomad4 ASJ

AF:

0.269

Gnomad4 EAS

AF:

0.615

Gnomad4 SAS

AF:

0.432

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.425

Gnomad4 OTH

AF:

0.405

Alfa

AF:

0.308

Hom.:

828

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 04, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.7

DANN

Benign

0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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