rs9421799

Variant names:

• chr10-47326532-C-A
• rs9421799
• NM_016204.4:c.*748C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-47326532-C-A
• chr10-47326532-C-G
• chr10-47326532-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016204.4(GDF2):​c.*748C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 152,114 control chromosomes in the GnomAD database, including 26,127 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 0.57 (26127 hom., cov: 33)
• Consequence: GDF2 NM_016204.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 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.*748C>A		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.*748C>A		3_prime_UTR	Exon 2 of 2	ENSP00000463051.1	Q9UK05

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86878 AN: 151996 Hom.: 26127 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.589

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.571 AC: 86903 AN: 152114 Hom.: 26127 Cov.: 33 AF XY: 0.573 AC XY: 42610 AN XY: 74354

African (AFR) AF: 0.370 AC: 15362 AN: 41502

American (AMR) AF: 0.655 AC: 10018 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2337 AN: 3472

East Asian (EAS) AF: 0.680 AC: 3516 AN: 5174

South Asian (SAS) AF: 0.500 AC: 2409 AN: 4818

European-Finnish (FIN) AF: 0.693 AC: 7332 AN: 10582

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.647 AC: 43957 AN: 67956

Other (OTH) AF: 0.584 AC: 1235 AN: 2114

Alfa AF: 0.629 Hom.: 10434

Bravo AF: 0.566

Asia WGS AF: 0.550 AC: 1917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.74
PhyloP100		-0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9421799; hg19: chr10-48412830;