NM_016204.4:c.*397A>C

Variant names:

• chr10-47326181-A-C
• rs34379100
• NM_016204.4:c.*397A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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), G2P, ClinGen
• hereditary hemorrhagic telangiectasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016204.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF2	NM_016204.4	MANE Select	c.*397A>C		3_prime_UTR	Exon 2 of 2	NP_057288.1	Q9UK05

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF2	ENST00000581492.3	TSL:1 MANE Select	c.*397A>C		3_prime_UTR	Exon 2 of 2	ENSP00000463051.1	Q9UK05

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

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: 18 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: 14 AN: 118

European-Non Finnish (NFE) AF: 0.179 AC: 2725 AN: 15244

Other (OTH) AF: 0.169 AC: 240 AN: 1418

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

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: 38 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13119 AN: 67996

Other (OTH) AF: 0.192 AC: 406 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.11
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

Other links and lift over

dbSNP: rs34379100; hg19: chr10-48413181;