rs263035

Variant names:

• chr3-183805869-A-G
• rs263035
• NM_018023.5:c.3785-997A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018023.5(YEATS2):​c.3785-997A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 151,546 control chromosomes in the GnomAD database, including 15,320 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15320 hom., cov: 29)
• Consequence: YEATS2 NM_018023.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710
• Publications: 13 publications found

Genes affected

YEATS2 (HGNC:25489): (YEATS domain containing 2) Summary: The protein encoded by this gene is a scaffolding subunit of the ATAC complex, which is a complex with acetyltransferase activity on histones H3 and H4. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2017]

YEATS2 Gene-Disease associations (from GenCC):

• benign adult familial myoclonic epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YEATS2	NM_018023.5	c.3785-997A>G		intron_variant	Intron 27 of 30	ENST00000305135.10	NP_060493.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YEATS2	ENST00000305135.10	c.3785-997A>G		intron_variant	Intron 27 of 30	1	NM_018023.5	ENSP00000306983.5
YEATS2	ENST00000472593.1	n.3213-997A>G		intron_variant	Intron 1 of 4	2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67614 AN: 151426 Hom.: 15320 Cov.: 29

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.446 AC: 67634 AN: 151546 Hom.: 15320 Cov.: 29 AF XY: 0.442 AC XY: 32690 AN XY: 74032

African (AFR) AF: 0.418 AC: 17258 AN: 41274

American (AMR) AF: 0.492 AC: 7497 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1711 AN: 3466

East Asian (EAS) AF: 0.508 AC: 2595 AN: 5108

South Asian (SAS) AF: 0.493 AC: 2369 AN: 4806

European-Finnish (FIN) AF: 0.326 AC: 3417 AN: 10486

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31267 AN: 67882

Other (OTH) AF: 0.489 AC: 1027 AN: 2100

Alfa AF: 0.452 Hom.: 2503

Bravo AF: 0.459

Asia WGS AF: 0.503 AC: 1749 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.041
DANN	Benign	0.45
PhyloP100		-0.71
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: rs263035; hg19: chr3-183523657; COSMIC: COSV59364916; COSMIC: COSV59364916;