20-33611108-AAC-TCA

Variant names:

• chr20-33611108-AAC-TCA
• NM_001032999.3:c.193_195delAACinsTCA
• CBFA2T2 p.Asn65Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001032999.3(CBFA2T2):​c.193_195delAACinsTCA​(p.Asn65Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N65K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CBFA2T2 NM_001032999.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00
• Publications: 0 publications found

Genes affected

CBFA2T2 (HGNC:1536): (CBFA2/RUNX1 partner transcriptional co-repressor 2) In acute myeloid leukemia, especially in the M2 subtype, the t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities. The translocation produces a chimeric gene made up of the 5'-region of the RUNX1 (AML1) gene fused to the 3'-region of the CBFA2T1 (MTG8) gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. The protein encoded by this gene binds to the AML1-MTG8 complex and may be important in promoting leukemogenesis. Several transcript variants are thought to exist for this gene, but the full-length natures of only three have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001032999.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBFA2T2	NM_001032999.3	MANE Select	c.193_195delAACinsTCA	p.Asn65Ser	missense	N/A	NP_001028171.1	O43439-5
	CBFA2T2	NM_005093.4		c.220_222delAACinsTCA	p.Asn74Ser	missense	N/A	NP_005084.1	O43439-1
	CBFA2T2	NM_001039709.2		c.133_135delAACinsTCA	p.Asn45Ser	missense	N/A	NP_001034798.1	O43439-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBFA2T2	ENST00000342704.11	TSL:1 MANE Select	c.193_195delAACinsTCA	p.Asn65Ser	missense	N/A	ENSP00000345810.6	O43439-5
	CBFA2T2	ENST00000346541.7	TSL:1	c.220_222delAACinsTCA	p.Asn74Ser	missense	N/A	ENSP00000262653.7	O43439-1
	CBFA2T2	ENST00000344201.7	TSL:1	c.133_135delAACinsTCA	p.Asn45Ser	missense	N/A	ENSP00000341865.3	O43439-3

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-32198914;