3-183810479-C-G

Variant names:

• chr3-183810479-C-G
• NM_018023.5:c.4165C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018023.5(YEATS2):​c.4165C>G​(p.Pro1389Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: YEATS2 NM_018023.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.11
• 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-AS1 (HGNC:41101): (YEATS2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.4165C>G	p.Pro1389Ala	missense	Exon 31 of 31	NP_060493.3
	YEATS2	NM_001351370.2		c.4168C>G	p.Pro1390Ala	missense	Exon 31 of 31	NP_001338299.1
	YEATS2	NM_001351369.2		c.4165C>G	p.Pro1389Ala	missense	Exon 31 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.4165C>G	p.Pro1389Ala	missense	Exon 31 of 31	ENSP00000306983.5	Q9ULM3
	YEATS2	ENST00000884732.1		c.4168C>G	p.Pro1390Ala	missense	Exon 31 of 31	ENSP00000554791.1
	YEATS2	ENST00000884736.1		c.4168C>G	p.Pro1390Ala	missense	Exon 32 of 32	ENSP00000554795.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	Benign	0.30
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.1
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.76
MutPred		0.50		Gain of sheet (P = 0.0344)
MVP		0.12
MPC		0.51
ClinPred		0.99	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.81
Mutation Taster		=29/71	disease causing

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

hg19: chr3-183528267;