17-42114921-G-A

Variant names:

• chr17-42114921-G-A
• rs17659391
• NM_021078.3:c.1990C>T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.35

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]

ACMG classification

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	c.1990C>T	p.Leu664Leu	synonymous_variant	Exon 13 of 18	ENST00000225916.10	NP_066564.2
KAT2A	NM_001376227.1	c.1990C>T	p.Leu664Leu	synonymous_variant	Exon 13 of 18		NP_001363156.1
KAT2A	XM_006721818.5	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	Appris	UniProt
KAT2A	ENST00000225916.10	c.1990C>T	p.Leu664Leu	synonymous_variant	Exon 13 of 18	1	NM_021078.3	ENSP00000225916.5
KAT2A	ENST00000465682.5	n.*1104C>T		non_coding_transcript_exon_variant	Exon 13 of 18	5		ENSP00000468390.1
KAT2A	ENST00000465682.5	n.*1104C>T		3_prime_UTR_variant	Exon 13 of 18	5		ENSP00000468390.1
KAT2A	ENST00000588759.1	n.193+33C>T		intron_variant	Intron 2 of 4	5		ENSP00000467324.1

Frequencies

GnomAD3 genomes AF: 0.0501 AC: 7626 AN: 152126 Hom.: 291 Cov.: 32

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

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.: 32 AF XY: 0.0649 AC XY: 47201 AN XY: 727084

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.: 32 AF XY: 0.0489 AC XY: 3642 AN XY: 74434

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: 25 AN: 3478

EpiCase AF: 0.0662

EpiControl AF: 0.0625

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	12
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

Other links and lift over

dbSNP: rs17659391; hg19: chr17-40266939;