3-20040509-GCTGCGGGGCAGGAGCCGGGGCAGGGGCCGGGCCCGGGGCGCTGCCCCCGCAGCCTGCGGCGCTTCCGCCCGCGCCCCCGCAGGGCTCCCCCTGCGCCGCTGCCGCCGGGGGCTCGGGCGC-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_003884.5(KAT2B):c.39_158del(p.Ala14_Gly53del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00111 in 1,031,618 control chromosomes in the GnomAD database, including 42 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0013 (41 hom.)
• Consequence: KAT2B NM_003884.5 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.67

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 3-20040509-GCTGCGGGGCAGGAGCCGGGGCAGGGGCCGGGCCCGGGGCGCTGCCCCCGCAGCCTGCGGCGCTTCCGCCCGCGCCCCCGCAGGGCTCCCCCTGCGCCGCTGCCGCCGGGGGCTCGGGCGC-G is Benign according to our data. Variant chr3-20040509-GCTGCGGGGCAGGAGCCGGGGCAGGGGCCGGGCCCGGGGCGCTGCCCCCGCAGCCTGCGGCGCTTCCGCCCGCGCCCCCGCAGGGCTCCCCCTGCGCCGCTGCCGCCGGGGGCTCGGGCGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 3044350.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KAT2B	NM_003884.5	c.39_158del	p.Ala14_Gly53del	inframe_deletion	1/18	ENST00000263754.5
KAT2B	XM_005265528.5	c.39_158del	p.Ala14_Gly53del	inframe_deletion	1/17
KAT2B	XM_047449147.1	c.-457_-338del		5_prime_UTR_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KAT2B	ENST00000263754.5	c.39_158del	p.Ala14_Gly53del	inframe_deletion	1/18	1	NM_003884.5	P1

Frequencies

GnomAD3 genomes AF: 0.000225 AC: 33 AN: 146972 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.0000734

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.000270

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000227

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00126 AC: 1111 AN: 884546 Hom.: 41 AF XY: 0.00129 AC XY: 533 AN XY: 412902

Gnomad4 AFR exome AF: 0.000704

Gnomad4 AMR exome AF: 0.00954

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000283

Gnomad4 FIN exome AF: 0.0134

Gnomad4 NFE exome AF: 0.00115

Gnomad4 OTH exome AF: 0.00259

GnomAD4 genome AF: 0.000224 AC: 33 AN: 147072 Hom.: 1 Cov.: 31 AF XY: 0.000168 AC XY: 12 AN XY: 71620

Gnomad4 AFR AF: 0.0000732

Gnomad4 AMR AF: 0.000270

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00116

Gnomad4 NFE AF: 0.000227

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000447 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

KAT2B-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 19, 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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1697691490; hg19: chr3-20082001;