5-37812820-GGT-G

Variant names:

• chr5-37812820-GGT-G
• rs141939066
• NM_000514.4:c.*2829_*2830delAC

Variant summary

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

The NM_000514.4(GDNF):​c.*2829_*2830delAC 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: not found (cov: 20)
• Consequence: GDNF NM_000514.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.675

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 rank	MANE	Protein	UniProt
GDNF	NM_000514.4	c.*2829_*2830delAC		3_prime_UTR_variant	Exon 3 of 3	ENST00000326524.7	NP_000505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDNF	ENST00000326524	c.*2829_*2830delAC		3_prime_UTR_variant	Exon 3 of 3	1	NM_000514.4	ENSP00000317145.2
GDNF	ENST00000344622.8	c.*2829_*2830delAC		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000339703.4
GDNF	ENST00000620847.1	c.*2829_*2830delAC		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000478722.1
GDNF-AS1	ENST00000637595.1	n.195-770_195-769delGT		intron_variant	Intron 1 of 11	5

Frequencies

GnomAD3 genomes Cov.: 20

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 20

Alfa AF: 0.291 Hom.: 583

Bravo AF: 0.276

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hirschsprung Disease, Dominant Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs141939066; hg19: chr5-37812922; COSMIC: COSV58479353; COSMIC: COSV58479353;