2-48346279-C-G

Variant names:

• chr2-48346279-C-G
• rs1671094577
• NM_002158.4:c.65C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002158.4(FOXN2):​c.65C>G​(p.Ala22Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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. A22V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOXN2 NM_002158.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2873824).

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.65C>G	p.Ala22Gly	missense	Exon 3 of 7	NP_002149.2
	FOXN2	NM_001375442.1		c.65C>G	p.Ala22Gly	missense	Exon 3 of 7	NP_001362371.1	P32314-1
	FOXN2	NM_001375443.1		c.65C>G	p.Ala22Gly	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.65C>G	p.Ala22Gly	missense	Exon 3 of 7	ENSP00000343633.3	P32314-1
	FOXN2	ENST00000872826.1		c.65C>G	p.Ala22Gly	missense	Exon 4 of 8	ENSP00000542885.1
	FOXN2	ENST00000872827.1		c.65C>G	p.Ala22Gly	missense	Exon 3 of 7	ENSP00000542886.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.36	D
MutationAssessor	Benign	1.1	L
PhyloP100		4.7
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.66	N
REVEL	Uncertain	0.34
Sift	Benign	0.058	T
Sift4G	Benign	0.21	T
Polyphen		0.52	P
Vest4		0.51
MutPred		0.20		Gain of catalytic residue at I21 (P = 0.084)
MVP		0.97
MPC		0.039
ClinPred		0.77	D
GERP RS		5.3
Varity_R		0.11
gMVP		0.20
Mutation Taster		=69/31	polymorphism

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: rs1671094577; hg19: chr2-48573418;