9-77019683-G-A

Variant names:

• chr9-77019683-G-A
• rs2063907614
• NM_001013735.1:c.29G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001013735.1(FOXB2):​c.29G>A​(p.Ser10Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,447,346 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S10G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FOXB2 NM_001013735.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.72
• Publications: 0 publications found

Genes affected

FOXB2 (HGNC:23315): (forkhead box B2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anatomical structure morphogenesis; cell differentiation; and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013735.1. 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
	FOXB2	NM_001013735.1	MANE Select	c.29G>A	p.Ser10Asn	missense	Exon 1 of 1	NP_001013757.1	Q5VYV0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXB2	ENST00000376708.1	TSL:6 MANE Select	c.29G>A	p.Ser10Asn	missense	Exon 1 of 1	ENSP00000365898.1	Q5VYV0
	FOXB2	ENST00000850987.1		c.29G>A	p.Ser10Asn	missense	Exon 1 of 1	ENSP00000521069.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1447346 Hom.: 0 Cov.: 33 AF XY: 0.00000139 AC XY: 1 AN XY: 718714

African (AFR) AF: 0.00 AC: 0 AN: 33058

American (AMR) AF: 0.00 AC: 0 AN: 42326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 38948

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105128

Other (OTH) AF: 0.00 AC: 0 AN: 59922

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Pathogenic	0.49	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	1.5	L
PhyloP100		9.7
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.48
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.080	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.25		Loss of phosphorylation at S10 (P = 0.0252)
MVP		0.98
ClinPred		0.94	D
GERP RS		4.4
PromoterAI		0.0017	Neutral
Varity_R		0.25
gMVP		0.42
Mutation Taster		=61/39	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: rs2063907614; hg19: chr9-79634599;