rs2255182

chr8-96152676-A-G

Variant summary

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

The NM_001001557.4(GDF6):c.407-7152T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,064 control chromosomes in the GnomAD database, including 15,730 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 0.45 (15730 hom., cov: 32)
• Consequence: GDF6 NM_001001557.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

Genes affected

GDF6 (HGNC:4221): (growth differentiation factor 6) 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 is required for normal formation of some bones and joints in the limbs, skull, and axial skeleton. Mutations in this gene are associated with Klippel-Feil syndrome, microphthalmia, and Leber congenital amaurosis. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDF6	NM_001001557.4	c.407-7152T>C		intron_variant		ENST00000287020.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDF6	ENST00000287020.7	c.407-7152T>C		intron_variant		1	NM_001001557.4	P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68124 AN: 151944 Hom.: 15724 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.448 AC: 68179 AN: 152064 Hom.: 15730 Cov.: 32 AF XY: 0.446 AC XY: 33130 AN XY: 74332

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.436

Alfa AF: 0.488 Hom.: 24203

Bravo AF: 0.431

Asia WGS AF: 0.373 AC: 1296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.038
Dann	Benign	0.32

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: rs2255182; hg19: chr8-97164904;