rs34379100

Positions:

• chr10-47326181-A-C
• chr10-47326181-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
GDF2	NM_016204.4	c.*397A>C		3_prime_UTR_variant	2/2	ENST00000581492.3	NP_057288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF2	ENST00000581492.3	c.*397A>C		3_prime_UTR_variant	2/2	1	NM_016204.4	ENSP00000463051.1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30362 AN: 152106 Hom.: 3207 Cov.: 33

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.: 0 AF XY: 0.166 AC XY: 1942 AN XY: 11694

Gnomad4 AFR exome AF: 0.260

Gnomad4 AMR exome AF: 0.0888

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.0147

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.200 AC: 30409 AN: 152224 Hom.: 3212 Cov.: 33 AF XY: 0.198 AC XY: 14726 AN XY: 74434

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0383

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.192

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
DANN	Benign	0.41

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

Other links and lift over

dbSNP: rs34379100; hg19: chr10-48413181;