rs80359867

Positions:

• chr8-27799639-C-CT

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001017420.3(ESCO2):​c.1597dup​(p.Cys533LeufsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ESCO2 NM_001017420.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.61

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-27799639-C-CT is Pathogenic according to our data. Variant chr8-27799639-C-CT is described in ClinVar as [Pathogenic]. Clinvar id is 21238.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESCO2	NM_001017420.3	c.1597dup	p.Cys533LeufsTer5	frameshift_variant	10/11	ENST00000305188.13	NP_001017420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESCO2	ENST00000305188.13	c.1597dup	p.Cys533LeufsTer5	frameshift_variant	10/11	1	NM_001017420.3	ENSP00000306999	P1
ESCO2	ENST00000522378.5	c.*572dup		3_prime_UTR_variant, NMD_transcript_variant	8/12	1		ENSP00000428928
ESCO2	ENST00000397418.4	c.541dup	p.Cys181LeufsTer5	frameshift_variant	5/7	5		ENSP00000380563
ESCO2	ENST00000518262.5			downstream_gene_variant		3		ENSP00000428959

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Roberts-SC phocomelia syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

curation

GeneReviews

Oct 02, 2008

- -

Computational scores

Source: dbNSFP v4.3

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: rs80359867; hg19: chr8-27657156;