Variant 17-42118011-ACTGAAGCTGAGGAGAGAGAGAGACGTCAGGGATGGGGGG-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PVS1_ModerateBP6_ModerateBA1

The ENST00000225916.10(KAT2A):c.1181-33_1186del variant causes a splice acceptor, coding sequence, intron change. The variant allele was found at a frequency of 0.0297 in 141,280 control chromosomes in the GnomAD database, including 144 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 144 hom., cov: 31)

Exomes 𝑓: 0.032 ( 2059 hom. )

Failed GnomAD Quality Control

Consequence

KAT2A
ENST00000225916.10 splice_acceptor, coding_sequence, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.25

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.043754973 fraction of the gene. Cryptic splice site detected, with MaxEntScore 12, offset of 0 (no position change), new splice context is: ttctctctctctctcctcAGctt. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BP6

Variant 17-42118011-ACTGAAGCTGAGGAGAGAGAGAGACGTCAGGGATGGGGGG-A is Benign according to our data. Variant chr17-42118011-ACTGAAGCTGAGGAGAGAGAGAGACGTCAGGGATGGGGGG-A is described in ClinVar as [Benign]. Clinvar id is 775163.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-42118011-ACTGAAGCTGAGGAGAGAGAGAGACGTCAGGGATGGGGGG-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
KAT2A	NM_021078.3 linkuse as main transcript	c.1181-33_1186del	splice_acceptor_variant, coding_sequence_variant, intron_variant	8/18	ENST00000225916.10	NP_066564.2
KAT2A	NM_001376227.1 linkuse as main transcript	c.1181-33_1186del	splice_acceptor_variant, coding_sequence_variant, intron_variant	8/18		NP_001363156.1
KAT2A	XM_006721818.5 linkuse as main transcript	c.98-33_103del	splice_acceptor_variant, coding_sequence_variant, intron_variant	3/13		XP_006721881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAT2A	ENST00000225916.10 linkuse as main transcript	c.1181-33_1186del		splice_acceptor_variant, coding_sequence_variant, intron_variant	8/18	1	NM_021078.3	ENSP00000225916	P1	Q92830-1
KAT2A	ENST00000465682.5 linkuse as main transcript	c.295-33_300del		splice_acceptor_variant, 3_prime_UTR_variant, intron_variant, NMD_transcript_variant	8/18	5		ENSP00000468390

Frequencies

GnomAD3 genomes

AF:

0.0296

AC:

4176

AN:

141172

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0799

Gnomad AMI

AF:

0.0102

Gnomad AMR

AF:

0.0159

Gnomad ASJ

AF:

0.0367

Gnomad EAS

AF:

0.0121

Gnomad SAS

AF:

0.0295

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.0357

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.0279

GnomAD3 exomes

AF:

0.0416

AC:

9143

AN:

219986

Hom.:

386

AF XY:

0.0425

AC XY:

5040

AN XY:

118662

show subpopulations

Gnomad AFR exome

AF:

0.0913

Gnomad AMR exome

AF:

0.0249

Gnomad ASJ exome

AF:

0.0386

Gnomad EAS exome

AF:

0.0106

Gnomad SAS exome

AF:

0.0458

Gnomad FIN exome

AF:

0.0337

Gnomad NFE exome

AF:

0.0457

Gnomad OTH exome

AF:

0.0417

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0324

AC:

46288

AN:

1429614

Hom.:

2059

AF XY:

0.0321

AC XY:

22748

AN XY:

708512

show subpopulations

Gnomad4 AFR exome

AF:

0.0822

Gnomad4 AMR exome

AF:

0.0142

Gnomad4 ASJ exome

AF:

0.0382

Gnomad4 EAS exome

AF:

0.0215

Gnomad4 SAS exome

AF:

0.0350

Gnomad4 FIN exome

AF:

0.0175

Gnomad4 NFE exome

AF:

0.0322

Gnomad4 OTH exome

AF:

0.0339

GnomAD4 genome

AF:

0.0297

AC:

4201

AN:

141280

Hom.:

144

Cov.:

AF XY:

0.0295

AC XY:

2038

AN XY:

69082

show subpopulations

Gnomad4 AFR

AF:

0.0800

Gnomad4 AMR

AF:

0.0159

Gnomad4 ASJ

AF:

0.0367

Gnomad4 EAS

AF:

0.0123

Gnomad4 SAS

AF:

0.0300

Gnomad4 FIN

AF:

0.0142

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.0325

Alfa

AF:

0.0248

Hom.:

Asia WGS

AF:

0.0640

AC:

222

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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