17-42114568-TCTGGGCCTGTTTGCGCTCAATCAG-T

Variant names:

• chr17-42114568-TCTGGGCCTGTTTGCGCTCAATCAG-T
• NM_021078.3:c.2032_2055delCTGATTGAGCGCAAACAGGCCCAG

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PM4 PP3 PP5_Moderate

The NM_021078.3(KAT2A):​c.2032_2055delCTGATTGAGCGCAAACAGGCCCAG​(p.Leu678_Gln685del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KAT2A NM_021078.3 conservative_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 10.0

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_021078.3.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 17-42114568-TCTGGGCCTGTTTGCGCTCAATCAG-T is Pathogenic according to our data. Variant chr17-42114568-TCTGGGCCTGTTTGCGCTCAATCAG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2627105.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAT2A	NM_021078.3	c.2032_2055delCTGATTGAGCGCAAACAGGCCCAG	p.Leu678_Gln685del	conservative_inframe_deletion	Exon 14 of 18	ENST00000225916.10	NP_066564.2
KAT2A	NM_001376227.1	c.2035_2058delCTGATTGAGCGCAAACAGGCCCAG	p.Leu679_Gln686del	conservative_inframe_deletion	Exon 14 of 18		NP_001363156.1
KAT2A	XM_006721818.5	c.952_975delCTGATTGAGCGCAAACAGGCCCAG	p.Leu318_Gln325del	conservative_inframe_deletion	Exon 9 of 13		XP_006721881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAT2A	ENST00000225916.10	c.2032_2055delCTGATTGAGCGCAAACAGGCCCAG	p.Leu678_Gln685del	conservative_inframe_deletion	Exon 14 of 18	1	NM_021078.3	ENSP00000225916.5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Pathogenic:1

-

Hadassah Hebrew University Medical Center

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr17-40266586;