chr3-183721927-C-G

Variant names:

• chr3-183721927-C-G
• rs768013253
• NM_018023.5:c.328C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018023.5(YEATS2):​c.328C>G​(p.Pro110Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YEATS2 NM_018023.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.66
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.835

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.328C>G	p.Pro110Ala	missense	Exon 5 of 31	NP_060493.3
	YEATS2	NM_001351370.2		c.328C>G	p.Pro110Ala	missense	Exon 5 of 31	NP_001338299.1
	YEATS2	NM_001351369.2		c.328C>G	p.Pro110Ala	missense	Exon 5 of 31	NP_001338298.1	Q9ULM3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YEATS2	ENST00000305135.10	TSL:1 MANE Select	c.328C>G	p.Pro110Ala	missense	Exon 5 of 31	ENSP00000306983.5	Q9ULM3
	YEATS2	ENST00000884732.1		c.328C>G	p.Pro110Ala	missense	Exon 5 of 31	ENSP00000554791.1
	YEATS2	ENST00000884736.1		c.328C>G	p.Pro110Ala	missense	Exon 6 of 32	ENSP00000554795.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.060	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.86
MutPred		0.41		Loss of loop (P = 0.0031)
MVP		0.31
MPC		0.33
ClinPred		0.98	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.67
gMVP		0.50
Mutation Taster		=31/69	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs768013253; hg19: chr3-183439715;