chr10-47310366-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004962.5(GDF10):c.890C>G(p.Pro297Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000871 in 1,606,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000069 ( 0 hom. )
Consequence
GDF10
NM_004962.5 missense
NM_004962.5 missense
Scores
4
3
Clinical Significance
Conservation
PhyloP100: 5.72
Genes affected
GDF10 (HGNC:4215): (growth differentiation factor 10) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This promotes neural repair after stroke. Additionally, this protein may act as a tumor suppressor and reduced expression of this gene is associated with oral cancer. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GDF10 | NM_004962.5 | c.890C>G | p.Pro297Arg | missense_variant | 2/3 | ENST00000580279.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GDF10 | ENST00000580279.2 | c.890C>G | p.Pro297Arg | missense_variant | 2/3 | 1 | NM_004962.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000131 AC: 3AN: 228802Hom.: 0 AF XY: 0.0000159 AC XY: 2AN XY: 125990
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GnomAD4 exome AF: 0.00000687 AC: 10AN: 1454768Hom.: 0 Cov.: 33 AF XY: 0.00000553 AC XY: 4AN XY: 723436
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2023 | The c.890C>G (p.P297R) alteration is located in exon 2 (coding exon 2) of the GDF10 gene. This alteration results from a C to G substitution at nucleotide position 890, causing the proline (P) at amino acid position 297 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Uncertain
D
Sift4G
Uncertain
D
Vest4
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at