Genetic Variant FOXN2:p.Asn181Thr (chr2-48359051-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002158.4(FOXN2):c.542A>C(p.Asn181Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,611,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N181S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

FOXN2
NM_002158.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.78

Publications

0 publications found

Variant links:

Genes affected

FOXN2 (HGNC:5281): (forkhead box N2) This gene encodes a forkhead domain binding protein and may function in the transcriptional regulation of the human T-cell leukemia virus long terminal repeat. [provided by RefSeq, Jul 2008]

FOXN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2246835).

BS2

High AC in GnomAd4 at 17 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002158.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXN2	NM_002158.4	MANE Select	c.542A>C	p.Asn181Thr	missense	Exon 4 of 7	NP_002149.2
FOXN2	NM_001375442.1		c.542A>C	p.Asn181Thr	missense	Exon 4 of 7	NP_001362371.1	P32314-1
FOXN2	NM_001375443.1		c.542A>C	p.Asn181Thr	missense	Exon 3 of 6	NP_001362372.1	P32314-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXN2	ENST00000340553.8	TSL:1 MANE Select	c.542A>C	p.Asn181Thr	missense	Exon 4 of 7	ENSP00000343633.3	P32314-1
FOXN2	ENST00000872826.1		c.542A>C	p.Asn181Thr	missense	Exon 5 of 8	ENSP00000542885.1
FOXN2	ENST00000872827.1		c.542A>C	p.Asn181Thr	missense	Exon 4 of 7	ENSP00000542886.1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000440

AC:

AN:

249900

AF XY:

0.0000296

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1459332

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726070

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

33390

American (AMR)

AF:

0.0000899

AC:

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39546

South Asian (SAS)

AF:

0.00

AC:

AN:

85946

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110522

Other (OTH)

AF:

0.0000498

AC:

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000112

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.000386

AC:

AN:

41444

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.22

MetaSVM

Uncertain

0.48

MutationAssessor

Benign

0.46

PhyloP100

6.8

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.18

REVEL

Uncertain

0.47

Sift

Benign

0.35

Sift4G

Benign

1.0

Polyphen

0.99

Vest4

0.42

MVP

0.97

MPC

0.097

ClinPred

0.10

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.44

Mutation Taster

=47/53

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over