GDNF p.Arg143Arg

Variant names:

• chr5-37815857-A-A
• NM_000514.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr5-37815858--
• chr5-37815860-T-G
• chr5-37815858-C-T
• chr5-37815858-CCT-ACG
• chr5-37815858-CCT-GCG
• chr5-37815858-CCT-TCG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000514.4(GDNF):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GDNF NM_000514.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843
• Publications: 0 publications found

Genes affected

GDNF (HGNC:4232): (glial cell derived neurotrophic factor) 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. The recombinant form of this protein, a highly conserved neurotrophic factor, was shown to promote the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. This protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. Mutations in this gene may be associated with Hirschsprung disease and Tourette syndrome. This gene encodes multiple protein isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]

GDNF-AS1 (HGNC:43592): (GDNF antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000514.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDNF	NM_000514.4	MANE Select	c.		exon_region	Exon 3 of 3	NP_000505.1	P39905-1
	GDNF	NM_001190468.1		c.		exon_region	Exon 3 of 3	NP_001177397.1	P39905-3
	GDNF	NM_001190469.1		c.		exon_region	Exon 3 of 3	NP_001177398.1	P39905-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDNF	ENST00000326524.7	TSL:1 MANE Select	c.		exon_region	Exon 3 of 3	ENSP00000317145.2	P39905-1
	GDNF	ENST00000427982.5	TSL:1	c.		exon_region	Exon 3 of 3	ENSP00000409007.1	P39905-3
	GDNF	ENST00000381826.8	TSL:1	c.		exon_region	Exon 3 of 3	ENSP00000371248.4	P39905-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-37815959;