8-27774626-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.25

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
ESCO2	NM_001017420.3	c.-17+19C>T		intron_variant		ENST00000305188.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESCO2	ENST00000305188.13	c.-17+19C>T		intron_variant		1	NM_001017420.3	P1
ESCO2	ENST00000522378.5	c.-17+19C>T		intron_variant, NMD_transcript_variant		1
ESCO2	ENST00000523566.5	c.-16-873C>T		intron_variant		3
ESCO2	ENST00000519637.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63439 AN: 151834 Hom.: 13580 Cov.: 32

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: 92 AN: 216 Hom.: 23 Cov.: 0 AF XY: 0.407 AC XY: 66 AN XY: 162

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.: 32 AF XY: 0.417 AC XY: 31009 AN XY: 74286

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:1

Revision: criteria provided, single submitter

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. -

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

Other links and lift over

dbSNP: rs2272730; hg19: chr8-27632143; COSMIC: COSV59416271; COSMIC: COSV59416271;