17-82519935-CGGGCGGCGGGGCCGG-C

Variant names:

• chr17-82519935-CGGGCGGCGGGGCCGG-C
• rs746176542
• NM_004514.4:c.73_87delGCCGGGGGCGGCGGG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 2P and 10B. PM4 BP6_Moderate BA1

The NM_004514.4(FOXK2):​c.73_87delGCCGGGGGCGGCGGG​(p.Ala25_Gly29del) variant causes a conservative 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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A25A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.080 (518 hom., cov: 27)
  • Exomes 𝑓: 0.088 (3248 hom.)
• Consequence: FOXK2 NM_004514.4 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.10
• 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
FOXK2	NM_004514.4	c.73_87delGCCGGGGGCGGCGGG	p.Ala25_Gly29del	conservative_inframe_deletion	Exon 1 of 9	ENST00000335255.10	NP_004505.2
FOXK2	XM_047435919.1	c.73_87delGCCGGGGGCGGCGGG	p.Ala25_Gly29del	conservative_inframe_deletion	Exon 1 of 9		XP_047291875.1
FOXK2	XM_047435920.1	c.73_87delGCCGGGGGCGGCGGG	p.Ala25_Gly29del	conservative_inframe_deletion	Exon 1 of 5		XP_047291876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXK2	ENST00000335255.10	c.73_87delGCCGGGGGCGGCGGG	p.Ala25_Gly29del	conservative_inframe_deletion	Exon 1 of 9	1	NM_004514.4	ENSP00000335677.5
FOXK2	ENST00000473637.6	n.73_87delGCCGGGGGCGGCGGG		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000436108.2
FOXK2	ENST00000527313.6	n.-41_-27delGGGCGGCGGGGCCGG		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

GnomAD2 exomes AF: 0.0278 AC: 3 AN: 108 AF XY: 0.0333

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

African (AFR) AF: 0.0805 AC: 1278 AN: 15876

American (AMR) AF: 0.191 AC: 229 AN: 1202

Ashkenazi Jewish (ASJ) AF: 0.0843 AC: 443 AN: 5258

East Asian (EAS) AF: 0.0513 AC: 192 AN: 3744

South Asian (SAS) AF: 0.0547 AC: 937 AN: 17134

European-Finnish (FIN) AF: 0.276 AC: 169 AN: 612

Middle Eastern (MID) AF: 0.106 AC: 175 AN: 1652

European-Non Finnish (NFE) AF: 0.0887 AC: 67836 AN: 764812

Other (OTH) AF: 0.0895 AC: 2469 AN: 27598

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

African (AFR) AF: 0.0720 AC: 2914 AN: 40466

American (AMR) AF: 0.109 AC: 1593 AN: 14638

Ashkenazi Jewish (ASJ) AF: 0.0690 AC: 233 AN: 3376

East Asian (EAS) AF: 0.0372 AC: 184 AN: 4942

South Asian (SAS) AF: 0.0523 AC: 247 AN: 4722

European-Finnish (FIN) AF: 0.0559 AC: 454 AN: 8116

Middle Eastern (MID) AF: 0.0893 AC: 25 AN: 280

European-Non Finnish (NFE) AF: 0.0865 AC: 5641 AN: 65208

Other (OTH) AF: 0.0980 AC: 196 AN: 2000

Alfa AF: 0.0169 Hom.: 7

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=196/4	polymorphism

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; COSMIC: COSV58882655; COSMIC: COSV58882655;