17-42114511-C-A

Variant names:

• chr17-42114511-C-A
• NM_021078.3:c.2113G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021078.3(KAT2A):​c.2113G>T​(p.Val705Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KAT2A NM_021078.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2292338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT2A	NM_021078.3	c.2113G>T	p.Val705Leu	missense_variant	Exon 14 of 18	ENST00000225916.10	NP_066564.2
KAT2A	NM_001376227.1	c.2116G>T	p.Val706Leu	missense_variant	Exon 14 of 18		NP_001363156.1
KAT2A	XM_006721818.5	c.1033G>T	p.Val345Leu	missense_variant	Exon 9 of 13		XP_006721881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT2A	ENST00000225916.10	c.2113G>T	p.Val705Leu	missense_variant	Exon 14 of 18	1	NM_021078.3	ENSP00000225916.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2113G>T (p.V705L) alteration is located in exon 14 (coding exon 14) of the KAT2A gene. This alteration results from a G to T substitution at nucleotide position 2113, causing the valine (V) at amino acid position 705 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.061
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.098
Sift	Uncertain	0.024	D
Sift4G	Benign	0.28	T
Polyphen		0.20	B
Vest4		0.51
MutPred		0.36		Gain of loop (P = 0.2045);
MVP		0.32
MPC		0.93
ClinPred		0.66	D
GERP RS		4.0
Varity_R		0.12
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-40266529;