8-21909368-AGA-CGC

Variant names:

• chr8-21909368-AGA-CGC
• NM_003974.4:c.1180_1182delTCTinsGCG
• DOK2 p.Ser394Ala

Variant summary

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

The NM_003974.4(DOK2):​c.1180_1182delTCTinsGCG​(p.Ser394Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Benign in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DOK2 NM_003974.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 0 publications found

Genes affected

DOK2 (HGNC:2991): (docking protein 2) The protein encoded by this gene is constitutively tyrosine phosphorylated in hematopoietic progenitors isolated from chronic myelogenous leukemia (CML) patients in the chronic phase. It may be a critical substrate for p210(bcr/abl), a chimeric protein whose presence is associated with CML. This encoded protein binds p120 (RasGAP) from CML cells. [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_003974.4. 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
	DOK2	NM_003974.4	MANE Select	c.1180_1182delTCTinsGCG	p.Ser394Ala	missense	N/A	NP_003965.2
	DOK2	NM_001401272.1		c.898_900delTCTinsGCG	p.Ser300Ala	missense	N/A	NP_001388201.1
	DOK2	NM_001317800.2		c.718_720delTCTinsGCG	p.Ser240Ala	missense	N/A	NP_001304729.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOK2	ENST00000276420.9	TSL:1 MANE Select	c.1180_1182delTCTinsGCG	p.Ser394Ala	missense	N/A	ENSP00000276420.4	O60496
	DOK2	ENST00000852540.1		c.1174_1176delTCTinsGCG	p.Ser392Ala	missense	N/A	ENSP00000522599.1
	DOK2	ENST00000852539.1		c.898_900delTCTinsGCG	p.Ser300Ala	missense	N/A	ENSP00000522598.1

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		2.0

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: chr8-21766879;