Genetic Variant NM_004514.4:c.73_87dupGCCGGGGGCGGCGGG (chr17-82519935-C-CGGGCGGCGGGGCCGG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM1PM4BS2

The NM_004514.4(FOXK2):c.73_87dupGCCGGGGGCGGCGGG(p.Ala25_Gly29dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 144,680 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00028 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000036 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXK2
NM_004514.4 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0200

Publications

0 publications found

Variant links:

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]

FOXK2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 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.

BS2

High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK2	NM_004514.4 link	c.73_87dupGCCGGGGGCGGCGGG	p.Ala25_Gly29dup	conservative_inframe_insertion	Exon 1 of 9	ENST00000335255.10	NP_004505.2	Q01167-1
FOXK2	XM_047435919.1 link	c.73_87dupGCCGGGGGCGGCGGG	p.Ala25_Gly29dup	conservative_inframe_insertion	Exon 1 of 9		XP_047291875.1
FOXK2	XM_047435920.1 link	c.73_87dupGCCGGGGGCGGCGGG	p.Ala25_Gly29dup	conservative_inframe_insertion	Exon 1 of 5		XP_047291876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXK2	ENST00000335255.10 link	c.73_87dupGCCGGGGGCGGCGGG	p.Ala25_Gly29dup	conservative_inframe_insertion	Exon 1 of 9	1	NM_004514.4	ENSP00000335677.5	Q01167-1
FOXK2	ENST00000473637.6 link	n.73_87dupGCCGGGGGCGGCGGG		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000436108.2	Q01167-2
FOXK2	ENST00000527313.6 link	n.-42_-41insGGGCGGCGGGGCCGG		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

144680

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000520

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000137

Gnomad ASJ

AF:

0.00296

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000422

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000613

Gnomad OTH

AF:

0.00101

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000358

AC:

AN:

837966

Hom.:

Cov.:

AF XY:

0.0000336

AC XY:

AN XY:

387462

show subpopulations

African (AFR)

AF:

0.000315

AC:

AN:

15876

American (AMR)

AF:

0.00

AC:

AN:

1202

Ashkenazi Jewish (ASJ)

AF:

0.000761

AC:

AN:

5256

East Asian (EAS)

AF:

0.00

AC:

AN:

3744

South Asian (SAS)

AF:

0.0000584

AC:

AN:

17136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1652

European-Non Finnish (NFE)

AF:

0.0000235

AC:

AN:

764884

Other (OTH)

AF:

0.0000725

AC:

AN:

27602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000283

AC:

AN:

144680

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

AN XY:

70312

show subpopulations

African (AFR)

AF:

0.000520

AC:

AN:

40412

American (AMR)

AF:

0.000137

AC:

AN:

14638

Ashkenazi Jewish (ASJ)

AF:

0.00296

AC:

AN:

3378

East Asian (EAS)

AF:

0.00

AC:

AN:

4960

South Asian (SAS)

AF:

0.000422

AC:

AN:

4744

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000613

AC:

AN:

65244

Other (OTH)

AF:

0.00101

AC:

AN:

1986

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.020

Mutation Taster

=86/14

polymorphism

(source)

Splicing

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

Publications

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NM_004514.4:c.73_87dupGCCGGGGGCGGCGGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over