chr1-47438424-C-G

Variant names:

• chr1-47438424-C-G
• rs964252467
• NM_004474.4:c.289C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004474.4(FOXD2):​c.289C>G​(p.Pro97Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. P97T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXD2 NM_004474.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.849
• Publications: 0 publications found

Genes affected

FOXD2 (HGNC:3803): (forkhead box D2) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.197579).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD2	NM_004474.4	c.289C>G	p.Pro97Ala	missense_variant	Exon 1 of 1	ENST00000334793.6	NP_004465.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD2	ENST00000334793.6	c.289C>G	p.Pro97Ala	missense_variant	Exon 1 of 1	6	NM_004474.4	ENSP00000335493.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 997538 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 469148

African (AFR) AF: 0.00 AC: 0 AN: 20120

American (AMR) AF: 0.00 AC: 0 AN: 5734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10596

East Asian (EAS) AF: 0.00 AC: 0 AN: 19786

South Asian (SAS) AF: 0.00 AC: 0 AN: 18758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2450

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 865304

Other (OTH) AF: 0.00 AC: 0 AN: 37672

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.64
DEOGEN2	Benign	0.057	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.42	T
M_CAP	Pathogenic	0.99	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.85
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.29
Sift	Benign	0.13	T
Sift4G	Benign	0.28	T
Polyphen		0.043	B
Vest4		0.12
MutPred		0.20		Gain of helix (P = 0.0325);
MVP		0.60
ClinPred		0.083	T
GERP RS		2.4
PromoterAI		-0.043	Neutral
Varity_R		0.083
gMVP		0.57
Mutation Taster		=86/14	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: rs964252467; hg19: chr1-47904096;