8-27792770-AAG-A

Position:

• chr8-27792770-AAG-A

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001017420.3(ESCO2):​c.1461_1462del​(p.Arg487SerfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ESCO2 NM_001017420.3 frameshift
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.80

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 10 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESCO2	NM_001017420.3	c.1461_1462del	p.Arg487SerfsTer19	frameshift_variant	9/11	ENST00000305188.13	NP_001017420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESCO2	ENST00000305188.13	c.1461_1462del	p.Arg487SerfsTer19	frameshift_variant	9/11	1	NM_001017420.3	ENSP00000306999	P1
ESCO2	ENST00000522378.5	c.*436_*437del		3_prime_UTR_variant, NMD_transcript_variant	7/12	1		ENSP00000428928
ESCO2	ENST00000397418.4	c.405_406del	p.Arg135SerfsTer19	frameshift_variant	4/7	5		ENSP00000380563
ESCO2	ENST00000518262.5	c.467+723_467+724del		intron_variant		3		ENSP00000428959

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Roberts-SC phocomelia syndrome Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs80359866; hg19: chr8-27650287;