rs2607872

Positions:

• chr10-47307670-G-A
• chr10-47307670-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000580279.2(GDF10):​c.320-2126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,218 control chromosomes in the GnomAD database, including 50,738 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 0.79 (50738 hom., cov: 33)
• Consequence: GDF10 ENST00000580279.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918

Genes affected

GDF10 (HGNC:4215): (growth differentiation factor 10) 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 promotes neural repair after stroke. Additionally, this protein may act as a tumor suppressor and reduced expression of this gene is associated with oral cancer. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDF10	NM_004962.5	c.320-2126G>A		intron_variant		ENST00000580279.2	NP_004953.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF10	ENST00000580279.2	c.320-2126G>A		intron_variant		1	NM_004962.5	ENSP00000464145	P1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119701 AN: 152100 Hom.: 50725 Cov.: 33

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.827

Gnomad FIN AF: 0.966

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.825

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.787 AC: 119751 AN: 152218 Hom.: 50738 Cov.: 33 AF XY: 0.790 AC XY: 58780 AN XY: 74442

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.923

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.828

Gnomad4 FIN AF: 0.966

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.826

Alfa AF: 0.893 Hom.: 29881

Bravo AF: 0.761

Asia WGS AF: 0.794 AC: 2763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.18

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: rs2607872; hg19: chr10-48431692;