5-37813583-TG-T

Position:

• chr5-37813583-TG-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000514.4(GDNF):​c.*2067del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000076 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GDNF NM_000514.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.60

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDNF	NM_000514.4	c.*2067del		3_prime_UTR_variant	3/3	ENST00000326524.7	NP_000505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDNF	ENST00000326524.7	c.*2067del		3_prime_UTR_variant	3/3	1	NM_000514.4	ENSP00000317145	P1
GDNF	ENST00000344622.8	c.*2067del		3_prime_UTR_variant	3/3	1		ENSP00000339703
GDNF	ENST00000620847.1	c.*2067del		3_prime_UTR_variant	3/3	1		ENSP00000478722
GDNF-AS1	ENST00000637595.1	n.195-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 11 AN: 144500 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0000762

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000690

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.000224

Gnomad FIN AF: 0.000104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000615

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 316 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000761 AC: 11 AN: 144612 Hom.: 0 Cov.: 0 AF XY: 0.0000710 AC XY: 5 AN XY: 70432

Gnomad4 AFR AF: 0.0000760

Gnomad4 AMR AF: 0.0000689

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000198

Gnomad4 SAS AF: 0.000224

Gnomad4 FIN AF: 0.000104

Gnomad4 NFE AF: 0.0000615

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hirschsprung Disease, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886060589; hg19: chr5-37813685;