NM_177559.3:c.1165_1167delGCTinsACA

Variant names:

• chr20-483970-AGC-TGT
• NM_177559.3:c.1165_1167delGCTinsACA
• CSNK2A1 p.Ala389Thr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_177559.3(CSNK2A1):​c.1165_1167delGCTinsACA​(p.Ala389Thr) 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 Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSNK2A1 NM_177559.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.86
• Publications: 0 publications found

Genes affected

CSNK2A1 (HGNC:2457): (casein kinase 2 alpha 1) Casein kinase II is a serine/threonine protein kinase that phosphorylates acidic proteins such as casein. It is involved in various cellular processes, including cell cycle control, apoptosis, and circadian rhythm. The kinase exists as a tetramer and is composed of an alpha, an alpha-prime, and two beta subunits. The alpha subunits contain the catalytic activity while the beta subunits undergo autophosphorylation. The protein encoded by this gene represents the alpha subunit. Multiple transcript variants encoding different protein isoforms have been found for this gene. [provided by RefSeq, Apr 2018]

CSNK2A1 Gene-Disease associations (from GenCC):

• Okur-Chung neurodevelopmental syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP2: Missense variant in the CSNK2A1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 28 curated pathogenic missense variants (we use a threshold of 10). The gene has 7 curated benign missense variants. Gene score misZ: 3.7123 (above the threshold of 3.09). Trascript score misZ: 5.3205 (above the threshold of 3.09). GenCC associations: The gene is linked to Okur-Chung neurodevelopmental syndrome, syndromic intellectual disability.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177559.3. 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
	CSNK2A1	NM_177559.3	MANE Select	c.1165_1167delGCTinsACA	p.Ala389Thr	missense	N/A	NP_808227.1	P68400-1
	CSNK2A1	NM_001362770.2		c.1165_1167delGCTinsACA	p.Ala389Thr	missense	N/A	NP_001349699.1	P68400-1
	CSNK2A1	NM_001362771.2		c.1165_1167delGCTinsACA	p.Ala389Thr	missense	N/A	NP_001349700.1	P68400-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2A1	ENST00000217244.9	TSL:1 MANE Select	c.1165_1167delGCTinsACA	p.Ala389Thr	missense	N/A	ENSP00000217244.3	P68400-1
	CSNK2A1	ENST00000349736.10	TSL:1	c.757_759delGCTinsACA	p.Ala253Thr	missense	N/A	ENSP00000339247.6	P68400-2
	CSNK2A1	ENST00000400227.8	TSL:1	c.1060+2404_1060+2406delGCTinsACA		intron	N/A	ENSP00000383086.3	E7EU96

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		5.9

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: chr20-464614;