3-183737365-A-G

Variant names:

• chr3-183737365-A-G
• rs262977
• NM_018023.5:c.924+536A>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.924+536A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,986 control chromosomes in the GnomAD database, including 13,155 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 0.41 (13155 hom., cov: 31)
• Consequence: YEATS2 NM_018023.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018023.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YEATS2	NM_018023.5	MANE Select	c.924+536A>G		intron	N/A	NP_060493.3
	YEATS2	NM_001351370.2		c.924+536A>G		intron	N/A	NP_001338299.1
	YEATS2	NM_001351369.2		c.924+536A>G		intron	N/A	NP_001338298.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YEATS2	ENST00000305135.10	TSL:1 MANE Select	c.924+536A>G		intron	N/A	ENSP00000306983.5
	YEATS2	ENST00000884732.1		c.924+536A>G		intron	N/A	ENSP00000554791.1
	YEATS2	ENST00000884736.1		c.924+536A>G		intron	N/A	ENSP00000554795.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61754 AN: 151868 Hom.: 13160 Cov.: 31

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.406 AC: 61759 AN: 151986 Hom.: 13155 Cov.: 31 AF XY: 0.402 AC XY: 29906 AN XY: 74306

African (AFR) AF: 0.294 AC: 12179 AN: 41456

American (AMR) AF: 0.478 AC: 7303 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1778 AN: 3466

East Asian (EAS) AF: 0.507 AC: 2619 AN: 5164

South Asian (SAS) AF: 0.499 AC: 2397 AN: 4808

European-Finnish (FIN) AF: 0.312 AC: 3295 AN: 10566

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30761 AN: 67940

Other (OTH) AF: 0.456 AC: 961 AN: 2106

Alfa AF: 0.447 Hom.: 7956

Bravo AF: 0.414

Asia WGS AF: 0.498 AC: 1733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.47
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs262977; hg19: chr3-183455153;