rs952924879

Variant names:

• chr1-47438362-G-A
• rs952924879
• NM_004474.4:c.227G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-47438362-G-A
• chr1-47438362-G-T

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.227G>A​(p.Gly76Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000664 in 150,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. G76V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., 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: 2.02
• Publications: 1 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=0.17969832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD2	NM_004474.4	c.227G>A	p.Gly76Asp	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.227G>A	p.Gly76Asp	missense_variant	Exon 1 of 1	6	NM_004474.4	ENSP00000335493.6

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150696 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1088062 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 515654

African (AFR) AF: 0.00 AC: 0 AN: 22756

American (AMR) AF: 0.00 AC: 0 AN: 8258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14278

East Asian (EAS) AF: 0.00 AC: 0 AN: 26242

South Asian (SAS) AF: 0.00 AC: 0 AN: 24022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3062

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 922906

Other (OTH) AF: 0.00 AC: 0 AN: 43738

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150696 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73554

African (AFR) AF: 0.00 AC: 0 AN: 41242

American (AMR) AF: 0.00 AC: 0 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3450

East Asian (EAS) AF: 0.00 AC: 0 AN: 5106

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67592

Other (OTH) AF: 0.00 AC: 0 AN: 2074

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	0.0015	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	1.0	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.0
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.020	N
REVEL	Benign	0.22
Sift	Benign	0.27	T
Sift4G	Benign	0.41	T
Polyphen		0.27	B
Vest4		0.094
MutPred		0.23		Loss of helix (P = 0.079);
MVP		0.76
ClinPred		0.073	T
GERP RS		1.5
PromoterAI		0.044	Neutral
Varity_R		0.074
gMVP		0.27
Mutation Taster		=97/3	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: rs952924879; hg19: chr1-47904034;