chr2-48346401-C-A

Variant names:

• chr2-48346401-C-A
• NM_002158.4:c.187C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002158.4(FOXN2):​c.187C>A​(p.His63Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOXN2 NM_002158.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.806

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN2	NM_002158.4	MANE Select	c.187C>A	p.His63Asn	missense	Exon 3 of 7	NP_002149.2
	FOXN2	NM_001375442.1		c.187C>A	p.His63Asn	missense	Exon 3 of 7	NP_001362371.1	P32314-1
	FOXN2	NM_001375443.1		c.187C>A	p.His63Asn	missense	Exon 2 of 6	NP_001362372.1	P32314-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXN2	ENST00000340553.8	TSL:1 MANE Select	c.187C>A	p.His63Asn	missense	Exon 3 of 7	ENSP00000343633.3	P32314-1
	FOXN2	ENST00000872826.1		c.187C>A	p.His63Asn	missense	Exon 4 of 8	ENSP00000542885.1
	FOXN2	ENST00000872827.1		c.187C>A	p.His63Asn	missense	Exon 3 of 7	ENSP00000542886.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.30	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-4.3	D
REVEL	Pathogenic	0.69
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.065	T
Polyphen		1.0	D
Vest4		0.71
MutPred		0.40		Gain of loop (P = 0.0435)
MVP		0.99
MPC		0.14
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.84
gMVP		0.42
Mutation Taster		=30/70	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr2-48573540;