rs148730910

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_016204.4(GDF2):​c.1017C>G​(p.Ile339Met) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I339I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

GDF2
NM_016204.4 missense

Scores

3
2
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20
Variant links:
Genes affected
GDF2 (HGNC:4217): (growth differentiation factor 2) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein regulates cartilage and bone development, angiogenesis and differentiation of cholinergic central nervous system neurons. Mutations in this gene are associated with hereditary hemorrhagic telangiectasia. [provided by RefSeq, Jul 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.889

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GDF2NM_016204.4 linkc.1017C>G p.Ile339Met missense_variant Exon 2 of 2 ENST00000581492.3 NP_057288.1 Q9UK05B2RC63

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GDF2ENST00000581492.3 linkc.1017C>G p.Ile339Met missense_variant Exon 2 of 2 1 NM_016204.4 ENSP00000463051.1 Q9UK05

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_noAF
Benign
-0.34
CADD
Benign
4.5
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.86
D
LIST_S2
Benign
0.73
T
MetaRNN
Pathogenic
0.89
D
Sift4G
Pathogenic
0.0
D
Vest4
0.84
gMVP
0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-48413851; API