10-47325761-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_ModeratePP5_ModerateBS2
The NM_016204.4(GDF2):c.1267G>A(p.Val423Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000516 in 1,549,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_016204.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000501 AC: 7AN: 1397686Hom.: 0 Cov.: 32 AF XY: 0.00000291 AC XY: 2AN XY: 687144
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
Telangiectasia, hereditary hemorrhagic, type 5 Pathogenic:1
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 423 of the GDF2 protein (p.Val423Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with pulmonary arterial hypertension (PMID: 30578397, 31727138). ClinVar contains an entry for this variant (Variation ID: 541539). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects GDF2 function (PMID: 30578397). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at