rs7923671

chr10-47324792-T-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.347-49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,345,820 control chromosomes in the GnomAD database, including 561,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (55947 hom., cov: 32)
  • Exomes 𝑓: 0.92 (505925 hom.)
• Consequence: GDF2 NM_016204.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.417

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=-0.82).
• BP6: Variant 10-47324792-T-C is Benign according to our data. Variant chr10-47324792-T-C is described in ClinVar as [Benign]. Clinvar id is 674697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF2	NM_016204.4	c.347-49T>C		intron_variant		ENST00000581492.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF2	ENST00000581492.3	c.347-49T>C		intron_variant		1	NM_016204.4	P1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129060 AN: 152080 Hom.: 55917 Cov.: 32

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.887

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.936

Gnomad OTH AF: 0.855

GnomAD3 exomes AF: 0.891 AC: 198295 AN: 222444 Hom.: 89028 AF XY: 0.898 AC XY: 108810 AN XY: 121106

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.870

Gnomad ASJ exome AF: 0.894

Gnomad EAS exome AF: 0.812

Gnomad SAS exome AF: 0.895

Gnomad FIN exome AF: 0.953

Gnomad NFE exome AF: 0.934

Gnomad OTH exome AF: 0.915

GnomAD4 exome AF: 0.919 AC: 1097201 AN: 1193622 Hom.: 505925 Cov.: 16 AF XY: 0.920 AC XY: 554712 AN XY: 603128

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.872

Gnomad4 ASJ exome AF: 0.893

Gnomad4 EAS exome AF: 0.862

Gnomad4 SAS exome AF: 0.896

Gnomad4 FIN exome AF: 0.953

Gnomad4 NFE exome AF: 0.935

Gnomad4 OTH exome AF: 0.897

GnomAD4 genome AF: 0.848 AC: 129138 AN: 152198 Hom.: 55947 Cov.: 32 AF XY: 0.851 AC XY: 63338 AN XY: 74442

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.880

Gnomad4 ASJ AF: 0.903

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.949

Gnomad4 NFE AF: 0.936

Gnomad4 OTH AF: 0.854

Alfa AF: 0.905 Hom.: 26548

Bravo AF: 0.832

Asia WGS AF: 0.844 AC: 2936 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	-0.82
Cadd	Benign	1.0
Dann	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7923671; hg19: chr10-48414570;