8-27775524-C-T

Variant names:

• chr8-27775524-C-T
• NM_001017420.3:c.10C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001017420.3(ESCO2):​c.10C>T​(p.Leu4Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ESCO2 NM_001017420.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.618
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055505753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESCO2	NM_001017420.3	c.10C>T	p.Leu4Phe	missense_variant	Exon 2 of 11	ENST00000305188.13	NP_001017420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESCO2	ENST00000305188.13	c.10C>T	p.Leu4Phe	missense_variant	Exon 2 of 11	1	NM_001017420.3	ENSP00000306999.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Roberts-SC phocomelia syndrome Uncertain:1

Feb 16, 2025

Natera, Inc.

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.3
DANN	Benign	0.95
DEOGEN2	Benign	0.019	T;T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.54	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.056	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	.;N;.
PhyloP100		0.62
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.88	N;N;N
REVEL	Benign	0.047
Sift	Benign	0.41	T;T;T
Sift4G	Benign	0.45	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.084
MutPred		0.18		Gain of methylation at K8 (P = 0.0686);Gain of methylation at K8 (P = 0.0686);Gain of methylation at K8 (P = 0.0686);
MVP		0.40
MPC		0.13
ClinPred		0.054	T
GERP RS		1.9
Varity_R		0.034
gMVP		0.092
Mutation Taster		=96/4	polymorphism

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

hg19: chr8-27633041;