8-21750589-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001495.5(GFRA2):c.793C>T(p.Arg265Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 1,588,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001495.5 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
GFRA2 | NM_001495.5 | c.793C>T | p.Arg265Trp | missense_variant, splice_region_variant | 4/9 | ENST00000524240.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GFRA2 | ENST00000524240.6 | c.793C>T | p.Arg265Trp | missense_variant, splice_region_variant | 4/9 | 1 | NM_001495.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152250Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000228 AC: 5AN: 219546Hom.: 0 AF XY: 0.0000167 AC XY: 2AN XY: 119512
GnomAD4 exome AF: 0.0000230 AC: 33AN: 1436550Hom.: 0 Cov.: 30 AF XY: 0.0000140 AC XY: 10AN XY: 713280
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74392
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2022 | The c.793C>T (p.R265W) alteration is located in exon 4 (coding exon 4) of the GFRA2 gene. This alteration results from a C to T substitution at nucleotide position 793, causing the arginine (R) at amino acid position 265 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at