rs1824449

Variant names:

• chr8-27784092-G-A
• rs1824449
• NM_001017420.3:c.1013+35G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001017420.3(ESCO2):​c.1013+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,599,720 control chromosomes in the GnomAD database, including 793,718 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73009 hom., cov: 31)
  • Exomes 𝑓: 1.0 (720709 hom.)
• Consequence: ESCO2 NM_001017420.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0560
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 8-27784092-G-A is Benign according to our data. Variant chr8-27784092-G-A is described in ClinVar as Benign. ClinVar VariationId is 257053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001017420.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESCO2	NM_001017420.3	MANE Select	c.1013+35G>A		intron	N/A	NP_001017420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESCO2	ENST00000305188.13	TSL:1 MANE Select	c.1013+35G>A		intron	N/A	ENSP00000306999.8
	ESCO2	ENST00000522378.5	TSL:1	n.862-3793G>A		intron	N/A	ENSP00000428928.1
	ESCO2	ENST00000518262.5	TSL:3	c.125+35G>A		intron	N/A	ENSP00000428959.1

Frequencies

GnomAD3 genomes AF: 0.979 AC: 148913 AN: 152160 Hom.: 72957 Cov.: 31

Gnomad AFR AF: 0.926

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.982

GnomAD2 exomes AF: 0.995 AC: 249514 AN: 250862 AF XY: 0.996

Gnomad AFR exome AF: 0.926

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.997

GnomAD4 exome AF: 0.998 AC: 1444337 AN: 1447442 Hom.: 720709 Cov.: 29 AF XY: 0.998 AC XY: 719887 AN XY: 721198

African (AFR) AF: 0.923 AC: 30580 AN: 33126

American (AMR) AF: 0.997 AC: 44515 AN: 44668

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26024 AN: 26024

East Asian (EAS) AF: 1.00 AC: 39498 AN: 39498

South Asian (SAS) AF: 1.00 AC: 85912 AN: 85936

European-Finnish (FIN) AF: 1.00 AC: 53272 AN: 53272

Middle Eastern (MID) AF: 0.996 AC: 5710 AN: 5732

European-Non Finnish (NFE) AF: 1.00 AC: 1099183 AN: 1099266

Other (OTH) AF: 0.995 AC: 59643 AN: 59920

GnomAD4 genome AF: 0.979 AC: 149024 AN: 152278 Hom.: 73009 Cov.: 31 AF XY: 0.980 AC XY: 72962 AN XY: 74456

African (AFR) AF: 0.926 AC: 38475 AN: 41542

American (AMR) AF: 0.992 AC: 15176 AN: 15304

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5172

South Asian (SAS) AF: 1.00 AC: 4827 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10612 AN: 10612

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68010 AN: 68030

Other (OTH) AF: 0.982 AC: 2074 AN: 2112

Alfa AF: 0.990 Hom.: 14231

Bravo AF: 0.976

Asia WGS AF: 0.996 AC: 3459 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Juberg-Hayward syndrome (1)
-	-	1	not specified (1)
-	-	1	Roberts-SC phocomelia syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.63
DANN	Benign	0.58
PhyloP100		-0.056
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1824449; hg19: chr8-27641609;