8-27780149-GTT-GTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001017420.3(ESCO2):c.862-15dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,227,570 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 33)
  • Exomes 𝑓: 0.012 (1 hom.)
• Consequence: ESCO2 NM_001017420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.907

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000376 (56/149124) while in subpopulation SAS AF= 0.00341 (16/4694). AF 95% confidence interval is 0.00214. There are 0 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESCO2	NM_001017420.3	c.862-15dup		intron_variant		ENST00000305188.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESCO2	ENST00000305188.13	c.862-15dup		intron_variant		1	NM_001017420.3	P1
ESCO2	ENST00000522378.5	c.861+2990dup		intron_variant, NMD_transcript_variant		1
ESCO2	ENST00000523910.1	n.661-15dup		intron_variant, non_coding_transcript_variant		3
ESCO2	ENST00000518262.5			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.000376 AC: 56 AN: 149016 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00108

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00341

Gnomad FIN AF: 0.000100

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000134

Gnomad OTH AF: 0.000978

GnomAD4 exome AF: 0.0116 AC: 12506 AN: 1078446 Hom.: 1 Cov.: 19 AF XY: 0.0111 AC XY: 6056 AN XY: 544418

Gnomad4 AFR exome AF: 0.00824

Gnomad4 AMR exome AF: 0.00751

Gnomad4 ASJ exome AF: 0.00866

Gnomad4 EAS exome AF: 0.00665

Gnomad4 SAS exome AF: 0.0112

Gnomad4 FIN exome AF: 0.00385

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.000376 AC: 56 AN: 149124 Hom.: 0 Cov.: 33 AF XY: 0.000523 AC XY: 38 AN XY: 72722

Gnomad4 AFR AF: 0.000271

Gnomad4 AMR AF: 0.00107

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00341

Gnomad4 FIN AF: 0.000100

Gnomad4 NFE AF: 0.000134

Gnomad4 OTH AF: 0.000968

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs375159544; hg19: chr8-27637666;