Variant 17-82520042-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004514.4(FOXK2):c.154C>T(p.Arg52Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0046 in 1,519,506 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0047 ( 22 hom. )

Consequence

FOXK2
NM_004514.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: 3.04

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008000493).

BP6

Variant 17-82520042-C-T is Benign according to our data. Variant chr17-82520042-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 619076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 551 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FOXK2	NM_004514.4 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	1/9	ENST00000335255.10
FOXK2	XM_047435919.1 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	1/9
FOXK2	XM_047435920.1 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXK2	ENST00000335255.10 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant	1/9	1	NM_004514.4	P1	Q01167-1
FOXK2	ENST00000473637.6 linkuse as main transcript	c.154C>T	p.Arg52Cys	missense_variant, NMD_transcript_variant	1/10	1			Q01167-2
FOXK2	ENST00000527313.6 linkuse as main transcript	n.66C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.00368

AC:

551

AN:

149720

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000975

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00677

Gnomad ASJ

AF:

0.00437

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00147

Gnomad FIN

AF:

0.00240

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00537

Gnomad OTH

AF:

0.00147

GnomAD3 exomes

AF:

0.00360

AC:

680

AN:

188702

Hom.:

AF XY:

0.00358

AC XY:

380

AN XY:

106088

show subpopulations

Gnomad AFR exome

AF:

0.00132

Gnomad AMR exome

AF:

0.00362

Gnomad ASJ exome

AF:

0.00319

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00174

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00513

Gnomad OTH exome

AF:

0.00463

GnomAD4 exome

AF:

0.00470

AC:

6444

AN:

1369692

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

3079

AN XY:

682122

show subpopulations

Gnomad4 AFR exome

AF:

0.00124

Gnomad4 AMR exome

AF:

0.00360

Gnomad4 ASJ exome

AF:

0.00302

Gnomad4 EAS exome

AF:

0.0000317

Gnomad4 SAS exome

AF:

0.00212

Gnomad4 FIN exome

AF:

0.00179

Gnomad4 NFE exome

AF:

0.00533

Gnomad4 OTH exome

AF:

0.00467

GnomAD4 genome

AF:

0.00368

AC:

551

AN:

149814

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

268

AN XY:

73096

show subpopulations

Gnomad4 AFR

AF:

0.000972

Gnomad4 AMR

AF:

0.00676

Gnomad4 ASJ

AF:

0.00437

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00147

Gnomad4 FIN

AF:

0.00240

Gnomad4 NFE

AF:

0.00537

Gnomad4 OTH

AF:

0.00145

Alfa

AF:

0.00525

Hom.:

Bravo

AF:

0.00415

ESP6500AA

AF:

0.000687

AC:

ESP6500EA

AF:

0.00631

AC:

ExAC

AF:

0.00360

AC:

432

ClinVar

Significance: Likely benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 21, 2018	- -

Premature ovarian insufficiency

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Reproductive Development, Murdoch Childrens Research Institute

Jan 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Benign

0.044

Eigen_PC

Benign

-0.016

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.64

MetaRNN

Benign

0.0080

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.23

Sift

Benign

0.047

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.34

MVP

0.48

MPC

2.5

ClinPred

0.035

GERP RS

1.5

Varity_R

0.29

gMVP

0.85

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over