8-21718897-C-G

Variant names:

• chr8-21718897-C-G
• rs13250096
• NM_001495.5:c.795-12856G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001495.5(GFRA2):​c.795-12856G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1294 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: GFRA2 NM_001495.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 3 publications found

Genes affected

GFRA2 (HGNC:4244): (GDNF family receptor alpha 2) Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are two structurally related, potent neurotrophic factors that play key roles in the control of neuron survival and differentiation. The protein encoded by this gene is a member of the GDNF receptor family. It is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor for both GDNF and NTN, and mediates activation of the RET tyrosine kinase receptor. This encoded protein acts preferentially as a receptor for NTN compared to its other family member, GDNF family receptor alpha 1. This gene is a candidate gene for RET-associated diseases. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001495.5. 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
	GFRA2	NM_001495.5	MANE Select	c.795-12856G>C		intron	N/A	NP_001486.4
	GFRA2	NM_001165038.2		c.480-12856G>C		intron	N/A	NP_001158510.1	O00451-3
	GFRA2	NM_001165039.2		c.396-12856G>C		intron	N/A	NP_001158511.1	O00451-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GFRA2	ENST00000524240.6	TSL:1 MANE Select	c.795-12856G>C		intron	N/A	ENSP00000428518.1	O00451-1
	GFRA2	ENST00000517892.5	TSL:1	c.480-12856G>C		intron	N/A	ENSP00000429979.1	O00451-3
	GFRA2	ENST00000518077.5	TSL:1	c.396-12856G>C		intron	N/A	ENSP00000429206.1	O00451-2

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18314 AN: 151552 Hom.: 1293 Cov.: 30

Gnomad AFR AF: 0.0713

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.113

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.121 AC: 18329 AN: 151670 Hom.: 1294 Cov.: 30 AF XY: 0.122 AC XY: 9026 AN XY: 74068

African (AFR) AF: 0.0714 AC: 2953 AN: 41360

American (AMR) AF: 0.110 AC: 1680 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3470

East Asian (EAS) AF: 0.121 AC: 621 AN: 5112

South Asian (SAS) AF: 0.0319 AC: 153 AN: 4792

European-Finnish (FIN) AF: 0.206 AC: 2168 AN: 10500

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9937 AN: 67888

Other (OTH) AF: 0.112 AC: 236 AN: 2104

Alfa AF: 0.0757 Hom.: 98

Bravo AF: 0.113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.66
PhyloP100		0.0070
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs13250096; hg19: chr8-21576409; COSMIC: COSV60781556;