dbSNP rs17581368: GFRA2:c.-36+84G>T (chr8-21804933-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000517328.5(GFRA2):c.-36+84G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,876 control chromosomes in the GnomAD database, including 11,675 homozygotes. 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 0.39 ( 11669 hom., cov: 31)

Exomes 𝑓: 0.40 ( 6 hom. )

Consequence

GFRA2
ENST00000517328.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.56

Publications

13 publications found

Variant links:

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]

GFRA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GFRA2	XM_047421687.1 link	c.-36+7298G>T		intron_variant	Intron 1 of 9		XP_047277643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GFRA2	ENST00000517328.5 link	c.-36+84G>T		intron_variant	Intron 2 of 10	5		ENSP00000429445.1

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58503

AN:

151678

Hom.:

11652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.396

Gnomad AMR

AF:

0.422

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.553

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.388

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.334

Gnomad OTH

AF:

0.343

GnomAD4 exome

AF:

0.400

AC:

AN:

Hom.:

AF XY:

0.464

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AF:

0.318

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.342

AC:

AN:

Other (OTH)

AF:

0.400

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.386

AC:

58548

AN:

151796

Hom.:

11669

Cov.:

AF XY:

0.392

AC XY:

29085

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.433

AC:

17890

AN:

41346

American (AMR)

AF:

0.423

AC:

6447

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

1330

AN:

3468

East Asian (EAS)

AF:

0.553

AC:

2843

AN:

5140

South Asian (SAS)

AF:

0.432

AC:

2078

AN:

4808

European-Finnish (FIN)

AF:

0.388

AC:

4093

AN:

10558

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.334

AC:

22706

AN:

67918

Other (OTH)

AF:

0.344

AC:

722

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1769

3537

5306

7074

8843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.348

Hom.:

41293

Bravo

AF:

0.387

Asia WGS

AF:

0.481

AC:

1675

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.015

(source)

DANN

Benign

0.47

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over