dbSNP rs17659391: KAT2A:p.Leu664Leu (chr17-42114921-G-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_021078.3(KAT2A):c.1990C>T(p.Leu664Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0652 in 1,613,768 control chromosomes in the GnomAD database, including 4,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 291 hom., cov: 32)

Exomes 𝑓: 0.067 ( 3892 hom. )

Consequence

KAT2A
NM_021078.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.35

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 17-42114921-G-A is Benign according to our data. Variant chr17-42114921-G-A is described in ClinVar as [Benign]. Clinvar id is 1249415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT2A	NM_021078.3 link	c.1990C>T	p.Leu664Leu	synonymous_variant	Exon 13 of 18	ENST00000225916.10	NP_066564.2	Q92830-1
KAT2A	NM_001376227.1 link	c.1990C>T	p.Leu664Leu	synonymous_variant	Exon 13 of 18		NP_001363156.1
KAT2A	XM_006721818.5 link	c.907C>T	p.Leu303Leu	synonymous_variant	Exon 8 of 13		XP_006721881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KAT2A	ENST00000225916.10 link	c.1990C>T	p.Leu664Leu	synonymous_variant	Exon 13 of 18	1	NM_021078.3	ENSP00000225916.5	Q92830-1
KAT2A	ENST00000465682.5 link	n.*1104C>T		non_coding_transcript_exon_variant	Exon 13 of 18	5		ENSP00000468390.1	K7ERS6
KAT2A	ENST00000465682.5 link	n.*1104C>T		3_prime_UTR_variant	Exon 13 of 18	5		ENSP00000468390.1	K7ERS6
KAT2A	ENST00000588759.1 link	n.193+33C>T		intron_variant	Intron 2 of 4	5		ENSP00000467324.1	K7EPC4

Frequencies

GnomAD3 genomes

AF:

0.0501

AC:

7626

AN:

152126

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0265

Gnomad ASJ

AF:

0.0242

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0762

Gnomad OTH

AF:

0.0283

GnomAD3 exomes

AF:

0.0517

AC:

13004

AN:

251290

Hom.:

547

AF XY:

0.0506

AC XY:

6878

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.0117

Gnomad AMR exome

AF:

0.0193

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.0754

Gnomad OTH exome

AF:

0.0569

GnomAD4 exome

AF:

0.0668

AC:

97665

AN:

1461524

Hom.:

3892

Cov.:

AF XY:

0.0649

AC XY:

47201

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.00986

Gnomad4 AMR exome

AF:

0.0197

Gnomad4 ASJ exome

AF:

0.0261

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0117

Gnomad4 FIN exome

AF:

0.121

Gnomad4 NFE exome

AF:

0.0761

Gnomad4 OTH exome

AF:

0.0598

GnomAD4 genome

AF:

0.0501

AC:

7622

AN:

152244

Hom.:

291

Cov.:

AF XY:

0.0489

AC XY:

3642

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0128

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.0242

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.117

Gnomad4 NFE

AF:

0.0762

Gnomad4 OTH

AF:

0.0270

Alfa

AF:

0.0620

Hom.:

451

Bravo

AF:

0.0423

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0662

EpiControl

AF:

0.0625

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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