8-27787355-C-T

Variant names:

• chr8-27787355-C-T
• rs17057863
• NM_001017420.3:c.1014-530C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001017420.3(ESCO2):​c.1014-530C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 150,966 control chromosomes in the GnomAD database, including 2,261 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2261 hom., cov: 30)
• Consequence: ESCO2 NM_001017420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• Roberts-SC phocomelia syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• Roberts syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESCO2	NM_001017420.3	c.1014-530C>T		intron_variant	Intron 5 of 10	ENST00000305188.13	NP_001017420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESCO2	ENST00000305188.13	c.1014-530C>T		intron_variant	Intron 5 of 10	1	NM_001017420.3	ENSP00000306999.8
ESCO2	ENST00000522378.5	n.862-530C>T		intron_variant	Intron 3 of 11	1		ENSP00000428928.1
ESCO2	ENST00000518262.5	c.126-530C>T		intron_variant	Intron 2 of 5	3		ENSP00000428959.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23264 AN: 150854 Hom.: 2261 Cov.: 30

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0844

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0979

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.154 AC: 23266 AN: 150966 Hom.: 2261 Cov.: 30 AF XY: 0.154 AC XY: 11344 AN XY: 73666

African (AFR) AF: 0.244 AC: 10017 AN: 41090

American (AMR) AF: 0.126 AC: 1912 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3470

East Asian (EAS) AF: 0.368 AC: 1888 AN: 5132

South Asian (SAS) AF: 0.195 AC: 933 AN: 4780

European-Finnish (FIN) AF: 0.0844 AC: 862 AN: 10218

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.0979 AC: 6642 AN: 67816

Other (OTH) AF: 0.161 AC: 337 AN: 2096

Alfa AF: 0.125 Hom.: 250

Bravo AF: 0.161

Asia WGS AF: 0.258 AC: 896 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.071
DANN	Benign	0.22
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17057863; hg19: chr8-27644872;