rs3781226

chr10-47323104-G-Achr10-47323104-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016204.4(GDF2):c.346+90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0821 in 820,276 control chromosomes in the GnomAD database, including 3,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.068 (457 hom., cov: 33)
  • Exomes 𝑓: 0.085 (2800 hom.)
• Consequence: GDF2 NM_016204.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.376

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-47323104-G-A is Benign according to our data. Variant chr10-47323104-G-A is described in ClinVar as [Benign]. Clinvar id is 1232776.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF2	NM_016204.4	c.346+90G>A		intron_variant		ENST00000581492.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF2	ENST00000581492.3	c.346+90G>A		intron_variant		1	NM_016204.4	P1

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10371 AN: 152186 Hom.: 459 Cov.: 33

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0747

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0970

Gnomad FIN AF: 0.0888

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.0766

GnomAD4 exome AF: 0.0854 AC: 57012 AN: 667972 Hom.: 2800 AF XY: 0.0866 AC XY: 29408 AN XY: 339518

Gnomad4 AFR exome AF: 0.0167

Gnomad4 AMR exome AF: 0.0582

Gnomad4 ASJ exome AF: 0.0961

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.0886

Gnomad4 FIN exome AF: 0.0864

Gnomad4 NFE exome AF: 0.0813

Gnomad4 OTH exome AF: 0.0807

GnomAD4 genome AF: 0.0680 AC: 10362 AN: 152304 Hom.: 457 Cov.: 33 AF XY: 0.0702 AC XY: 5226 AN XY: 74462

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.0746

Gnomad4 ASJ AF: 0.0979

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.0967

Gnomad4 FIN AF: 0.0888

Gnomad4 NFE AF: 0.0837

Gnomad4 OTH AF: 0.0758

Alfa AF: 0.0796 Hom.: 283

Bravo AF: 0.0641

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	13
Dann	Benign	0.75

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: rs3781226; hg19: chr10-48416258;