8-27775350-T-G

Position:

• chr8-27775350-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001017420.3(ESCO2):​c.-16-149T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 702,244 control chromosomes in the GnomAD database, including 265,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56591 hom., cov: 32)
  • Exomes 𝑓: 0.87 (208777 hom.)
• Consequence: ESCO2 NM_001017420.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.826

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 8-27775350-T-G is Benign according to our data. Variant chr8-27775350-T-G is described in ClinVar as [Benign]. Clinvar id is 1254162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESCO2	NM_001017420.3	c.-16-149T>G		intron_variant		ENST00000305188.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESCO2	ENST00000305188.13	c.-16-149T>G		intron_variant		1	NM_001017420.3	P1
ESCO2	ENST00000522378.5	c.-16-149T>G		intron_variant, NMD_transcript_variant		1
ESCO2	ENST00000519637.1	c.-16-149T>G		intron_variant		3
ESCO2	ENST00000523566.5	c.-16-149T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130924 AN: 152054 Hom.: 56531 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.876

GnomAD4 exome AF: 0.870 AC: 478493 AN: 550072 Hom.: 208777 AF XY: 0.867 AC XY: 255656 AN XY: 294834

Gnomad4 AFR exome AF: 0.824

Gnomad4 AMR exome AF: 0.938

Gnomad4 ASJ exome AF: 0.863

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.836

Gnomad4 FIN exome AF: 0.846

Gnomad4 NFE exome AF: 0.862

Gnomad4 OTH exome AF: 0.876

GnomAD4 genome AF: 0.861 AC: 131044 AN: 152172 Hom.: 56591 Cov.: 32 AF XY: 0.862 AC XY: 64146 AN XY: 74404

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.848

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.879

Alfa AF: 0.857 Hom.: 7963

Bravo AF: 0.868

Asia WGS AF: 0.943 AC: 3281 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.34

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: rs2006937; hg19: chr8-27632867;