17-82586006-C-G

Variant names:

• chr17-82586006-C-G
• rs200809204
• NM_004514.4:c.1382C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004514.4(FOXK2):​c.1382C>G​(p.Ser461Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S461L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOXK2 NM_004514.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.39
• Publications: 3 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]

ENSG00000262147 (HGNC:58306):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK2	NM_004514.4	c.1382C>G	p.Ser461Trp	missense_variant	Exon 7 of 9	ENST00000335255.10	NP_004505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXK2	ENST00000335255.10	c.1382C>G	p.Ser461Trp	missense_variant	Exon 7 of 9	1	NM_004514.4	ENSP00000335677.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.031
Eigen_PC	Benign	-0.087
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.4
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.013	D
Polyphen		0.98	D
Vest4		0.53
MutPred		0.37		Loss of disorder (P = 6e-04);
MVP		0.84
MPC		0.36
ClinPred		0.94	D
GERP RS		4.3
PromoterAI		-0.043	Neutral
Varity_R		0.23
gMVP		0.39

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: rs200809204; hg19: chr17-80543882;