dbSNP rs9303326: KAT2A:p.Leu719Leu (chr17-42114374-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021078.3(KAT2A):c.2155T>C(p.Leu719Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,613,928 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 28 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 27 hom. )

Consequence

KAT2A
NM_021078.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.771

Variant links:

Genes affected

KAT2A (HGNC:4201): (lysine acetyltransferase 2A) KAT2A, or GCN5, is a histone acetyltransferase (HAT) that functions primarily as a transcriptional activator. It also functions as a repressor of NF-kappa-B (see MIM 164011) by promoting ubiquitination of the NF-kappa-B subunit RELA (MIM 164014) in a HAT-independent manner (Mao et al., 2009 [PubMed 19339690]).[supplied by OMIM, Sep 2009]

KAT2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 17-42114374-A-G is Benign according to our data. Variant chr17-42114374-A-G is described in ClinVar as [Benign]. Clinvar id is 773591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.771 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00997 (1517/152108) while in subpopulation AFR AF= 0.033 (1369/41464). AF 95% confidence interval is 0.0316. There are 28 homozygotes in gnomad4. There are 722 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1517 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT2A	NM_021078.3 link	c.2155T>C	p.Leu719Leu	synonymous_variant	Exon 15 of 18	ENST00000225916.10	NP_066564.2	Q92830-1
KAT2A	NM_001376227.1 link	c.2158T>C	p.Leu720Leu	synonymous_variant	Exon 15 of 18		NP_001363156.1
KAT2A	XM_006721818.5 link	c.1075T>C	p.Leu359Leu	synonymous_variant	Exon 10 of 13		XP_006721881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT2A	ENST00000225916.10 link	c.2155T>C	p.Leu719Leu	synonymous_variant	Exon 15 of 18	1	NM_021078.3	ENSP00000225916.5		Q92830-1

Frequencies

GnomAD3 genomes

AF:

0.00997

AC:

1516

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.00815

GnomAD3 exomes

AF:

0.00319

AC:

802

AN:

251450

Hom.:

AF XY:

0.00257

AC XY:

349

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.0365

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.000601

Gnomad NFE exome

AF:

0.00105

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00197

AC:

2885

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00181

AC XY:

1314

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0367

Gnomad4 AMR exome

AF:

0.00204

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.00121

Gnomad4 OTH exome

AF:

0.00283

GnomAD4 genome

AF:

0.00997

AC:

1517

AN:

152108

Hom.:

Cov.:

AF XY:

0.00971

AC XY:

722

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0330

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00358

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

2.1

DANN

Benign

0.77

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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