chr10-47322871-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate
The NM_016204.4(GDF2):c.203G>T(p.Arg68Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,614,026 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R68H) has been classified as Uncertain significance.
Frequency
Consequence
NM_016204.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GDF2 | NM_016204.4 | c.203G>T | p.Arg68Leu | missense_variant | 1/2 | ENST00000581492.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GDF2 | ENST00000581492.3 | c.203G>T | p.Arg68Leu | missense_variant | 1/2 | 1 | NM_016204.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461848Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727212
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74346
ClinVar
Submissions by phenotype
Telangiectasia, hereditary hemorrhagic, type 5 Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 22, 2023 | 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. Experimental studies have shown that this missense change affects GDF2 function (PMID: 23972370). 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. ClinVar contains an entry for this variant (Variation ID: 88651). This missense change has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (PMID: 23972370). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 68 of the GDF2 protein (p.Arg68Leu). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 05, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at