19-18388613-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004864.4(GDF15):c.605A>G(p.His202Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000076 in 1,447,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H202D) has been classified as Likely benign.
Frequency
Consequence
NM_004864.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GDF15 | NM_004864.4 | c.605A>G | p.His202Arg | missense_variant | 2/2 | ENST00000252809.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GDF15 | ENST00000252809.3 | c.605A>G | p.His202Arg | missense_variant | 2/2 | 1 | NM_004864.4 | P1 | |
GDF15 | ENST00000595973.3 | c.605A>G | p.His202Arg | missense_variant | 3/3 | 5 | P1 | ||
GDF15 | ENST00000597765.2 | c.605A>G | p.His202Arg | missense_variant | 3/3 | 4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000760 AC: 11AN: 1447290Hom.: 0 Cov.: 35 AF XY: 0.00000556 AC XY: 4AN XY: 719808
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 29, 2021 | The c.605A>G (p.H202R) alteration is located in exon 2 (coding exon 2) of the GDF15 gene. This alteration results from a A to G substitution at nucleotide position 605, causing the histidine (H) at amino acid position 202 to be replaced by an arginine (R). 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