Genetic Variant YEATS2:p.Ser96Phe (chr3-183718588-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_018023.5(YEATS2):c.287C>T(p.Ser96Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000335 in 1,610,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

YEATS2
NM_018023.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73

Publications

1 publications found

Variant links:

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

YEATS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21170211).

BS2

High AC in GnomAd4 at 11 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YEATS2	NM_018023.5	MANE Select	c.287C>T	p.Ser96Phe	missense	Exon 4 of 31	NP_060493.3
YEATS2	NM_001351370.2		c.287C>T	p.Ser96Phe	missense	Exon 4 of 31	NP_001338299.1
YEATS2	NM_001351369.2		c.287C>T	p.Ser96Phe	missense	Exon 4 of 31	NP_001338298.1	Q9ULM3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
YEATS2	ENST00000305135.10	TSL:1 MANE Select	c.287C>T	p.Ser96Phe	missense	Exon 4 of 31	ENSP00000306983.5	Q9ULM3
YEATS2	ENST00000884732.1		c.287C>T	p.Ser96Phe	missense	Exon 4 of 31	ENSP00000554791.1
YEATS2	ENST00000884736.1		c.287C>T	p.Ser96Phe	missense	Exon 5 of 32	ENSP00000554795.1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

243756

AF XY:

0.0000227

show subpopulations

Gnomad AFR exome

AF:

0.0000655

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000902

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000295

AC:

AN:

1457844

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

725060

show subpopulations

African (AFR)

AF:

0.000749

AC:

AN:

33386

American (AMR)

AF:

0.0000226

AC:

AN:

44202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39580

South Asian (SAS)

AF:

0.00

AC:

AN:

85394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000991

AC:

AN:

1110216

Other (OTH)

AF:

0.0000996

AC:

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41454

American (AMR)

AF:

0.000131

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.018

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.8

PhyloP100

4.7

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.084

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.041

Polyphen

0.81

Vest4

0.29

MutPred

0.38

Gain of sheet (P = 0.0266)

MVP

0.068

MPC

0.21

ClinPred

0.44

GERP RS

5.7

Varity_R

0.18

gMVP

0.33

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over