rs9971293

Variant names:

• chr10-47324813-A-G
• rs9971293
• NM_016204.4:c.347-28A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-47324813-A-G
• chr10-47324813-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016204.4(GDF2):​c.347-28A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 1,495,310 control chromosomes in the GnomAD database, including 6,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1157 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5692 hom.)
• Consequence: GDF2 NM_016204.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.372
• Publications: 3 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), ClinGen, G2P
• hereditary hemorrhagic telangiectasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-47324813-A-G is Benign according to our data. Variant chr10-47324813-A-G is described in ClinVar as Benign. ClinVar VariationId is 1296410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF2	NM_016204.4	c.347-28A>G		intron_variant	Intron 1 of 1	ENST00000581492.3	NP_057288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF2	ENST00000581492.3	c.347-28A>G		intron_variant	Intron 1 of 1	1	NM_016204.4	ENSP00000463051.1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16380 AN: 152114 Hom.: 1153 Cov.: 33

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0613

Gnomad ASJ AF: 0.0571

Gnomad EAS AF: 0.00809

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.0942

GnomAD2 exomes AF: 0.0864 AC: 20507 AN: 237432 AF XY: 0.0904

Gnomad AFR exome AF: 0.206

Gnomad AMR exome AF: 0.0493

Gnomad ASJ exome AF: 0.0571

Gnomad EAS exome AF: 0.00859

Gnomad FIN exome AF: 0.0629

Gnomad NFE exome AF: 0.0743

Gnomad OTH exome AF: 0.0808

GnomAD4 exome AF: 0.0820 AC: 110088 AN: 1343078 Hom.: 5692 Cov.: 19 AF XY: 0.0847 AC XY: 57026 AN XY: 673000

African (AFR) AF: 0.209 AC: 6518 AN: 31134

American (AMR) AF: 0.0510 AC: 2262 AN: 44362

Ashkenazi Jewish (ASJ) AF: 0.0562 AC: 1409 AN: 25078

East Asian (EAS) AF: 0.00501 AC: 196 AN: 39098

South Asian (SAS) AF: 0.182 AC: 15155 AN: 83152

European-Finnish (FIN) AF: 0.0606 AC: 2957 AN: 48786

Middle Eastern (MID) AF: 0.0932 AC: 517 AN: 5550

European-Non Finnish (NFE) AF: 0.0756 AC: 76329 AN: 1009384

Other (OTH) AF: 0.0839 AC: 4745 AN: 56534

GnomAD4 genome AF: 0.108 AC: 16409 AN: 152232 Hom.: 1157 Cov.: 33 AF XY: 0.108 AC XY: 8016 AN XY: 74438

African (AFR) AF: 0.202 AC: 8403 AN: 41514

American (AMR) AF: 0.0613 AC: 938 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0571 AC: 198 AN: 3466

East Asian (EAS) AF: 0.00811 AC: 42 AN: 5180

South Asian (SAS) AF: 0.178 AC: 861 AN: 4824

European-Finnish (FIN) AF: 0.0548 AC: 582 AN: 10616

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0753 AC: 5122 AN: 68010

Other (OTH) AF: 0.101 AC: 213 AN: 2114

Alfa AF: 0.0882 Hom.: 278

Bravo AF: 0.110

Asia WGS AF: 0.135 AC: 469 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.1
DANN	Benign	0.81
PhyloP100		-0.37

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

Other links and lift over

dbSNP: rs9971293; hg19: chr10-48414549;