dbSNP rs34379100: GDF2:c.*397A>C (chr10-47326181-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_016204.4(GDF2):c.*397A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 175,600 control chromosomes in the GnomAD database, including 3,592 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 0.20 ( 3212 hom., cov: 33)

Exomes 𝑓: 0.16 ( 380 hom. )

Consequence

GDF2
NM_016204.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.59

Publications

10 publications found

Variant links:

Genes affected

GDF2 (HGNC:4217): (growth differentiation factor 2) 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 regulates cartilage and bone development, angiogenesis and differentiation of cholinergic central nervous system neurons. Mutations in this gene are associated with hereditary hemorrhagic telangiectasia. [provided by RefSeq, Jul 2016]

GDF2 Gene-Disease associations (from GenCC):

pulmonary arterial hypertension
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
telangiectasia, hereditary hemorrhagic, type 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
telangiectasia, hereditary hemorrhagic, type 5
Inheritance: AD, Unknown, AR Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P
hereditary hemorrhagic telangiectasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GDF2 links:

Genome browser will be placed here

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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF2	NM_016204.4 link	c.*397A>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000581492.3	NP_057288.1	Q9UK05B2RC63

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF2	ENST00000581492.3 link	c.*397A>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_016204.4	ENSP00000463051.1		Q9UK05

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30362

AN:

152106

Hom.:

3207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.270

Gnomad AMI

AF:

0.219

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.0384

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.187

GnomAD4 exome

AF:

0.161

AC:

3769

AN:

23376

Hom.:

380

Cov.:

AF XY:

0.166

AC XY:

1942

AN XY:

11694

show subpopulations

African (AFR)

AF:

0.260

AC:

204

AN:

786

American (AMR)

AF:

0.0888

AC:

187

AN:

2106

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

115

AN:

732

East Asian (EAS)

AF:

0.0147

AC:

AN:

1224

South Asian (SAS)

AF:

0.183

AC:

125

AN:

682

European-Finnish (FIN)

AF:

0.132

AC:

141

AN:

1066

Middle Eastern (MID)

AF:

0.119

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.179

AC:

2725

AN:

15244

Other (OTH)

AF:

0.169

AC:

240

AN:

1418

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

144

289

433

578

722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.200

AC:

30409

AN:

152224

Hom.:

3212

Cov.:

AF XY:

0.198

AC XY:

14726

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.270

AC:

11192

AN:

41512

American (AMR)

AF:

0.147

AC:

2247

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

496

AN:

3472

East Asian (EAS)

AF:

0.0383

AC:

199

AN:

5192

South Asian (SAS)

AF:

0.223

AC:

1075

AN:

4826

European-Finnish (FIN)

AF:

0.136

AC:

1438

AN:

10612

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.193

AC:

13119

AN:

67996

Other (OTH)

AF:

0.192

AC:

406

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1220

2439

3659

4878

6098

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.192

Hom.:

554

Bravo

AF:

0.201

Asia WGS

AF:

0.167

AC:

581

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.11

(source)

DANN

Benign

0.41

PhyloP100

-1.6

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

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rs34379100

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