NM_005251.3:c.20T>A

Variant names:

• chr16-86567355-T-A
• rs745506389
• NM_005251.3:c.20T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005251.3(FOXC2):​c.20T>A​(p.Val7Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,696 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FOXC2 NM_005251.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.61

Genes affected

FOXC2 (HGNC:3801): (forkhead box C2) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in the development of mesenchymal tissues. [provided by RefSeq, Jul 2008]

FOXC2-AS1 (HGNC:50665): (FOXC2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 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
FOXC2	NM_005251.3	c.20T>A	p.Val7Glu	missense_variant	Exon 1 of 1	ENST00000649859.1	NP_005242.1
FOXC2-AS1	NR_125795.1	n.145+262A>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXC2	ENST00000649859.1	c.20T>A	p.Val7Glu	missense_variant	Exon 1 of 1		NM_005251.3	ENSP00000497759.1
FOXC2-AS1	ENST00000563280.3	n.231+262A>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249242 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135384

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460696 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726678

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.78	D;D
Eigen	Benign	0.11
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	.;D
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Benign	2.0	M;M
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.9	.;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.011	.;D
Polyphen		0.59	P;P
Vest4		0.73
MutPred		0.38		Gain of disorder (P = 0.0168);Gain of disorder (P = 0.0168);
MVP		0.97
ClinPred		0.90	D
GERP RS		3.5
Varity_R		0.60
gMVP		0.77

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

Other links and lift over

dbSNP: rs745506389; hg19: chr16-86600961;