NM_004514.4:c.58_87dupGCCGGGGGCGGCGGGGCCGGGGGCGGCGGG

Variant names:

• chr17-82519935-C-CGGGCGGCGGGGCCGGGGGCGGCGGGGCCGG
• rs746176542
• NM_004514.4:c.58_87dupGCCGGGGGCGGCGGGGCCGGGGGCGGCGGG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM1 PM4

The NM_004514.4(FOXK2):​c.58_87dupGCCGGGGGCGGCGGGGCCGGGGGCGGCGGG​(p.Ala20_Gly29dup) variant causes a conservative inframe insertion 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 INS_BIG, 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.

• Frequency: Genomes: not found (cov: 27)
• Consequence: FOXK2 NM_004514.4 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 0 publications found

Genes affected

FOXK2 (HGNC:6036): (forkhead box K2) The protein encoded by this gene contains a fork head DNA binding domain. This protein can bind to the purine-rich motifs of the HIV long terminal repeat (LTR), and to the similar purine-rich motif in the interleukin 2 (IL2) promoter. It may be involved in the regulation of viral and cellular promoter elements. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity FOXK2_HUMAN
• PM4: Nonframeshift variant in NON repetitive region in NM_004514.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK2	NM_004514.4	c.58_87dupGCCGGGGGCGGCGGGGCCGGGGGCGGCGGG	p.Ala20_Gly29dup	conservative_inframe_insertion	Exon 1 of 9	ENST00000335255.10	NP_004505.2
FOXK2	XM_047435919.1	c.58_87dupGCCGGGGGCGGCGGGGCCGGGGGCGGCGGG	p.Ala20_Gly29dup	conservative_inframe_insertion	Exon 1 of 9		XP_047291875.1
FOXK2	XM_047435920.1	c.58_87dupGCCGGGGGCGGCGGGGCCGGGGGCGGCGGG	p.Ala20_Gly29dup	conservative_inframe_insertion	Exon 1 of 5		XP_047291876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXK2	ENST00000335255.10	c.58_87dupGCCGGGGGCGGCGGGGCCGGGGGCGGCGGG	p.Ala20_Gly29dup	conservative_inframe_insertion	Exon 1 of 9	1	NM_004514.4	ENSP00000335677.5
FOXK2	ENST00000473637.6	n.58_87dupGCCGGGGGCGGCGGGGCCGGGGGCGGCGGG		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000436108.2
FOXK2	ENST00000527313.6	n.-42_-41insGGGCGGCGGGGCCGGGGGCGGCGGGGCCGG		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome Cov.: 5

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.020

Splicing

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

Other links and lift over

dbSNP: rs746176542; hg19: chr17-80477811;