17-82519963-C-T

Variant names:

• chr17-82519963-C-T
• rs888679273
• NM_004514.4:c.75C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004514.4(FOXK2):​c.75C>T​(p.Ala25Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000104 in 960,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A25A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: FOXK2 NM_004514.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.274 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK2	NM_004514.4	c.75C>T	p.Ala25Ala	synonymous_variant	Exon 1 of 9	ENST00000335255.10	NP_004505.2
FOXK2	XM_047435919.1	c.75C>T	p.Ala25Ala	synonymous_variant	Exon 1 of 9		XP_047291875.1
FOXK2	XM_047435920.1	c.75C>T	p.Ala25Ala	synonymous_variant	Exon 1 of 5		XP_047291876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXK2	ENST00000335255.10	c.75C>T	p.Ala25Ala	synonymous_variant	Exon 1 of 9	1	NM_004514.4	ENSP00000335677.5
FOXK2	ENST00000473637.6	n.75C>T		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000436108.2
FOXK2	ENST00000527313.6	n.-14C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD2 exomes AF: 0.0000518 AC: 1 AN: 19300 AF XY: 0.0000829

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000113

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000104 AC: 1 AN: 960944 Hom.: 0 Cov.: 29 AF XY: 0.00000220 AC XY: 1 AN XY: 454474

African (AFR) AF: 0.00 AC: 0 AN: 18862

American (AMR) AF: 0.00 AC: 0 AN: 5102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9786

East Asian (EAS) AF: 0.00 AC: 0 AN: 15668

South Asian (SAS) AF: 0.00 AC: 0 AN: 22558

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2316

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839902

Other (OTH) AF: 0.00 AC: 0 AN: 34744

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		0.27
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs888679273; hg19: chr17-80477839;