8-27780149-GTT-GT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001017420.3(ESCO2):c.862-15del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00195 in 1,276,292 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (5 hom.)
• Consequence: ESCO2 NM_001017420.3 intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.907

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00455 (679/149158) while in subpopulation AFR AF= 0.0152 (617/40658). AF 95% confidence interval is 0.0142. There are 5 homozygotes in gnomad4. There are 321 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESCO2	NM_001017420.3	c.862-15del		intron_variant		ENST00000305188.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESCO2	ENST00000305188.13	c.862-15del		intron_variant		1	NM_001017420.3	P1
ESCO2	ENST00000522378.5	c.861+2990del		intron_variant, NMD_transcript_variant		1
ESCO2	ENST00000523910.1	n.661-15del		intron_variant, non_coding_transcript_variant		3
ESCO2	ENST00000518262.5			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.00454 AC: 676 AN: 149050 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000300

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000164

Gnomad OTH AF: 0.00391

GnomAD4 exome AF: 0.00161 AC: 1814 AN: 1127134 Hom.: 5 Cov.: 19 AF XY: 0.00148 AC XY: 844 AN XY: 569656

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.00191

Gnomad4 ASJ exome AF: 0.000323

Gnomad4 EAS exome AF: 0.000263

Gnomad4 SAS exome AF: 0.000993

Gnomad4 FIN exome AF: 0.000555

Gnomad4 NFE exome AF: 0.00128

Gnomad4 OTH exome AF: 0.00235

GnomAD4 genome AF: 0.00455 AC: 679 AN: 149158 Hom.: 5 Cov.: 33 AF XY: 0.00441 AC XY: 321 AN XY: 72736

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.000292

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000300

Gnomad4 NFE AF: 0.000164

Gnomad4 OTH AF: 0.00387

Alfa AF: 0.00414 Hom.: 0

Bravo AF: 0.00530

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 08, 2013

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs375159544; hg19: chr8-27637666;