Variant 3-20040662-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_003884.5(KAT2B):c.185G>A(p.Gly62Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,526,918 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

KAT2B
NM_003884.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.14

Variant links:

Genes affected

KAT2B (HGNC:8638): (lysine acetyltransferase 2B) CBP and p300 are large nuclear proteins that bind to many sequence-specific factors involved in cell growth and/or differentiation, including c-jun and the adenoviral oncoprotein E1A. The protein encoded by this gene associates with p300/CBP. It has in vitro and in vivo binding activity with CBP and p300, and competes with E1A for binding sites in p300/CBP. It has histone acetyl transferase activity with core histones and nucleosome core particles, indicating that this protein plays a direct role in transcriptional regulation. [provided by RefSeq, Jul 2008]

KAT2B links:

KAT2B (HGNC:):

KAT2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066883564).

BP6

Variant 3-20040662-G-A is Benign according to our data. Variant chr3-20040662-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3035151.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 154 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAT2B	NM_003884.5 linkuse as main transcript	c.185G>A	p.Gly62Asp	missense_variant	1/18	ENST00000263754.5	NP_003875.3	Q92831
KAT2B	XM_005265528.5 linkuse as main transcript	c.185G>A	p.Gly62Asp	missense_variant	1/17		XP_005265585.1
KAT2B	XM_047449147.1 linkuse as main transcript	c.-311G>A		5_prime_UTR_variant	1/20		XP_047305103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT2B	ENST00000263754.5 linkuse as main transcript	c.185G>A	p.Gly62Asp	missense_variant	1/18	1	NM_003884.5	ENSP00000263754.4		Q92831
KAT2B	ENST00000426228.1 linkuse as main transcript	n.-36G>A		upstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

154

AN:

151506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000766

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00186

Gnomad OTH

AF:

0.000963

GnomAD3 exomes

AF:

0.00132

AC:

181

AN:

136946

Hom.:

AF XY:

0.00112

AC XY:

AN XY:

78782

show subpopulations

Gnomad AFR exome

AF:

0.000226

Gnomad AMR exome

AF:

0.0000915

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000135

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000940

Gnomad NFE exome

AF:

0.00283

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00144

AC:

1986

AN:

1375304

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

977

AN XY:

682402

show subpopulations

Gnomad4 AFR exome

AF:

0.000176

Gnomad4 AMR exome

AF:

0.000119

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000318

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00176

Gnomad4 OTH exome

AF:

0.000636

GnomAD4 genome

AF:

0.00102

AC:

154

AN:

151614

Hom.:

Cov.:

AF XY:

0.000891

AC XY:

AN XY:

74070

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000766

Gnomad4 NFE

AF:

0.00186

Gnomad4 OTH

AF:

0.000953

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.000865

ExAC

AF:

0.00106

AC:

119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

KAT2B-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 20, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.51

M_CAP

Benign

0.040

MetaRNN

Benign

0.0067

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.83

REVEL

Benign

0.058

Sift

Benign

0.17

Sift4G

Uncertain

0.057

Polyphen

0.52

Vest4

0.19

MVP

0.23

MPC

0.58

ClinPred

0.033

GERP RS

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over