Variant 8-21693326-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001495.5(GFRA2):c.1347G>A(p.Ser449=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00929 in 1,613,534 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0081 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0094 ( 79 hom. )

Consequence

GFRA2
NM_001495.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.206

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 8-21693326-C-T is Benign according to our data. Variant chr8-21693326-C-T is described in ClinVar as [Benign]. Clinvar id is 778357.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.206 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GFRA2	NM_001495.5 linkuse as main transcript	c.1347G>A	p.Ser449=	synonymous_variant	9/9	ENST00000524240.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GFRA2	ENST00000524240.6 linkuse as main transcript	c.1347G>A	p.Ser449=	synonymous_variant	9/9	1	NM_001495.5	P1	O00451-1

Frequencies

GnomAD3 genomes

AF:

0.00814

AC:

1238

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00672

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00970

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00749

AC:

1848

AN:

246726

Hom.:

AF XY:

0.00734

AC XY:

984

AN XY:

134078

show subpopulations

Gnomad AFR exome

AF:

0.00628

Gnomad AMR exome

AF:

0.00880

Gnomad ASJ exome

AF:

0.0107

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00395

Gnomad NFE exome

AF:

0.0107

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00941

AC:

13756

AN:

1461386

Hom.:

Cov.:

AF XY:

0.00914

AC XY:

6644

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.00750

Gnomad4 AMR exome

AF:

0.00920

Gnomad4 ASJ exome

AF:

0.00865

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.00459

Gnomad4 NFE exome

AF:

0.0108

Gnomad4 OTH exome

AF:

0.00914

GnomAD4 genome

AF:

0.00814

AC:

1238

AN:

152148

Hom.:

Cov.:

AF XY:

0.00792

AC XY:

589

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.00670

Gnomad4 AMR

AF:

0.00969

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00742

Hom.:

Bravo

AF:

0.00952

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 29, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.7

DANN

Benign

0.71

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over