10-47322792-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016204.4(GDF2):c.124G>T(p.Gly42Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,618 control chromosomes in the GnomAD database, with no homozygous occurrence. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G42G) has been classified as Likely benign.
Frequency
Consequence
NM_016204.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GDF2 | NM_016204.4 | c.124G>T | p.Gly42Trp | missense_variant | 1/2 | ENST00000581492.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GDF2 | ENST00000581492.3 | c.124G>T | p.Gly42Trp | missense_variant | 1/2 | 1 | NM_016204.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251004Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135788
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461444Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726980
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74348
ClinVar
Submissions by phenotype
Telangiectasia, hereditary hemorrhagic, type 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 02, 2023 | This variant is present in population databases (rs782015913, gnomAD 0.01%). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. This variant has not been reported in the literature in individuals affected with GDF2-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 42 of the GDF2 protein (p.Gly42Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at