rs9421799

chr10-47326532-C-Achr10-47326532-C-Gchr10-47326532-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF2	NM_016204.4	c.*748C>A		3_prime_UTR_variant	2/2	ENST00000581492.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF2	ENST00000581492.3	c.*748C>A		3_prime_UTR_variant	2/2	1	NM_016204.4	P1

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

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.584

Alfa AF: 0.637 Hom.: 8285

Bravo AF: 0.566

Asia WGS AF: 0.550 AC: 1917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9421799; hg19: chr10-48412830;