8-27775312-C-T

Position:

• chr8-27775312-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001017420.3(ESCO2):​c.-16-187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,928 control chromosomes in the GnomAD database, including 6,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.28 (6657 hom., cov: 32)
• Consequence: ESCO2 NM_001017420.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-27775312-C-T is Benign according to our data. Variant chr8-27775312-C-T is described in ClinVar as [Benign]. Clinvar id is 1278193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESCO2	NM_001017420.3	c.-16-187C>T		intron_variant		ENST00000305188.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESCO2	ENST00000305188.13	c.-16-187C>T		intron_variant		1	NM_001017420.3	P1
ESCO2	ENST00000522378.5	c.-16-187C>T		intron_variant, NMD_transcript_variant		1
ESCO2	ENST00000519637.1	c.-16-187C>T		intron_variant		3
ESCO2	ENST00000523566.5	c.-16-187C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42501 AN: 151810 Hom.: 6660 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.280 AC: 42525 AN: 151928 Hom.: 6657 Cov.: 32 AF XY: 0.282 AC XY: 20951 AN XY: 74238

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.423

Gnomad4 EAS AF: 0.0170

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.305

Alfa AF: 0.227 Hom.: 698

Bravo AF: 0.269

Asia WGS AF: 0.132 AC: 463 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	-0.92
CADD	Benign	0.058
DANN	Benign	0.69

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: rs961334; hg19: chr8-27632829;