Variant 2-20667543-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_182828.4(GDF7):c.304A>G(p.Arg102Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000391 in 1,458,990 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00040 ( 10 hom. )

Consequence

GDF7
NM_182828.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

GDF7 (HGNC:4222): (growth differentiation factor 7) 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. This protein may play a role in the differentiation of tendon cells and spinal cord interneurons. A mutation in this gene may be associated with increased risk for Barrett's esophagus and esophageal adenocarcinoma. [provided by RefSeq, Sep 2016]

GDF7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006655723).

BP6

Variant 2-20667543-A-G is Benign according to our data. Variant chr2-20667543-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2650707.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF7	NM_182828.4 linkuse as main transcript	c.304A>G	p.Arg102Gly	missense_variant	1/2	ENST00000272224.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF7	ENST00000272224.5 linkuse as main transcript	c.304A>G	p.Arg102Gly	missense_variant	1/2	1	NM_182828.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000293

AC:

AN:

150398

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000660

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00883

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00116

AC:

122

AN:

104794

Hom.:

AF XY:

0.00139

AC XY:

AN XY:

61124

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000126

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00738

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000198

Gnomad OTH exome

AF:

0.000850

GnomAD4 exome

AF:

0.000402

AC:

526

AN:

1308482

Hom.:

Cov.:

AF XY:

0.000543

AC XY:

352

AN XY:

647926

show subpopulations

Gnomad4 AFR exome

AF:

0.0000752

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00664

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000278

Gnomad4 OTH exome

AF:

0.000527

GnomAD4 genome

AF:

0.000292

AC:

AN:

150508

Hom.:

Cov.:

AF XY:

0.000462

AC XY:

AN XY:

73546

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000659

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00885

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000864

AC:

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

GDF7: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.20

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0067

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.93

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

0.020

REVEL

Benign

0.068

Sift

Benign

0.30

Sift4G

Benign

0.33

Polyphen

0.41

Vest4

0.12

MutPred

0.43

Gain of catalytic residue at R102 (P = 0.0067);

MVP

0.57

ClinPred

0.056

GERP RS

2.7

Varity_R

0.095

gMVP

0.28

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