chr20-35433944-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_000557.5(GDF5):c.1471G>A(p.Glu491Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,990 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 Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. E491E) has been classified as Likely benign.
Frequency
Consequence
NM_000557.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GDF5 | NM_000557.5 | c.1471G>A | p.Glu491Lys | missense_variant | 2/2 | ENST00000374369.8 | |
GDF5-AS1 | NR_161326.1 | n.228C>T | non_coding_transcript_exon_variant | 2/2 | |||
GDF5 | NM_001319138.2 | c.1471G>A | p.Glu491Lys | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GDF5 | ENST00000374369.8 | c.1471G>A | p.Glu491Lys | missense_variant | 2/2 | 1 | NM_000557.5 | P1 | |
GDF5 | ENST00000374372.1 | c.1471G>A | p.Glu491Lys | missense_variant | 4/4 | 1 | P1 | ||
GDF5-AS1 | ENST00000374375.1 | n.228C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251440Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135892
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461806Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727218
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74326
ClinVar
Submissions by phenotype
Symphalangism, proximal, 1B Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2006 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at