rs12252199

chr10-47323088-G-Achr10-47323088-G-T

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+74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,057,058 control chromosomes in the GnomAD database, including 10,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1829 hom., cov: 32)
  • Exomes 𝑓: 0.13 (8245 hom.)
• Consequence: GDF2 NM_016204.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.64

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=-0.8).
• BP6: Variant 10-47323088-G-A is Benign according to our data. Variant chr10-47323088-G-A is described in ClinVar as [Benign]. Clinvar id is 674696.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF2	NM_016204.4	c.346+74G>A		intron_variant		ENST00000581492.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF2	ENST00000581492.3	c.346+74G>A		intron_variant		1	NM_016204.4	P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22109 AN: 152088 Hom.: 1823 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0945

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00846

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.129 AC: 117111 AN: 904850 Hom.: 8245 AF XY: 0.131 AC XY: 59445 AN XY: 453820

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.0760

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.00476

Gnomad4 SAS exome AF: 0.186

Gnomad4 FIN exome AF: 0.0911

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.146 AC: 22157 AN: 152208 Hom.: 1829 Cov.: 32 AF XY: 0.144 AC XY: 10683 AN XY: 74416

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.0945

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00848

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.0882

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.148

Alfa AF: 0.121 Hom.: 669

Bravo AF: 0.149

Asia WGS AF: 0.142 AC: 494 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

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.3
Dann	Benign	0.59

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: rs12252199; hg19: chr10-48416274;