chr17-82519935-CGGGCGGCGGGGCCGG-C

Position:

• chr17-82519935-CGGGCGGCGGGGCCGG-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_004514.4(FOXK2):​c.73_87del​(p.Ala25_Gly29del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 982,526 control chromosomes in the GnomAD database, including 3,766 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.080 (518 hom., cov: 27)
  • Exomes 𝑓: 0.088 (3248 hom.)
• Consequence: FOXK2 NM_004514.4 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.10

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

Verdict is Benign. Variant got -8 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_004514.4.
• BP6: Variant 17-82519935-CGGGCGGCGGGGCCGG-C is Benign according to our data. Variant chr17-82519935-CGGGCGGCGGGGCCGG-C is described in ClinVar as [Likely_benign]. Clinvar id is 770801.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXK2	NM_004514.4	c.73_87del	p.Ala25_Gly29del	inframe_deletion	1/9	ENST00000335255.10
FOXK2	XM_047435919.1	c.73_87del	p.Ala25_Gly29del	inframe_deletion	1/9
FOXK2	XM_047435920.1	c.73_87del	p.Ala25_Gly29del	inframe_deletion	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXK2	ENST00000335255.10	c.73_87del	p.Ala25_Gly29del	inframe_deletion	1/9	1	NM_004514.4	P1
FOXK2	ENST00000473637.6	c.73_87del	p.Ala25_Gly29del	inframe_deletion, NMD_transcript_variant	1/10	1
FOXK2	ENST00000527313.6			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 11581 AN: 144618 Hom.: 518 Cov.: 27

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0690

Gnomad EAS AF: 0.0373

Gnomad SAS AF: 0.0521

Gnomad FIN AF: 0.0559

Gnomad MID AF: 0.0921

Gnomad NFE AF: 0.0865

Gnomad OTH AF: 0.0987

GnomAD3 exomes AF: 0.0278 AC: 3 AN: 108 Hom.: 0 AF XY: 0.0333 AC XY: 2 AN XY: 60

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0469

GnomAD4 exome AF: 0.0880 AC: 73728 AN: 837888 Hom.: 3248 AF XY: 0.0886 AC XY: 34320 AN XY: 387426

Gnomad4 AFR exome AF: 0.0805

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.0843

Gnomad4 EAS exome AF: 0.0513

Gnomad4 SAS exome AF: 0.0547

Gnomad4 FIN exome AF: 0.276

Gnomad4 NFE exome AF: 0.0887

Gnomad4 OTH exome AF: 0.0895

GnomAD4 genome AF: 0.0801 AC: 11588 AN: 144638 Hom.: 518 Cov.: 27 AF XY: 0.0783 AC XY: 5506 AN XY: 70316

Gnomad4 AFR AF: 0.0720

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0690

Gnomad4 EAS AF: 0.0372

Gnomad4 SAS AF: 0.0523

Gnomad4 FIN AF: 0.0559

Gnomad4 NFE AF: 0.0865

Gnomad4 OTH AF: 0.0980

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs746176542; hg19: chr17-80477811;