8-96143132-CCT-C

Position:

• chr8-96143132-CCT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001001557.4(GDF6):​c.*1429_*1430delAG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 152,344 control chromosomes in the GnomAD database, including 121 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (121 hom., cov: 32)
  • Exomes 𝑓: 0.031 (0 hom.)
• Consequence: GDF6 NM_001001557.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.198

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 -10 ACMG points.

• BP6: Variant 8-96143132-CCT-C is Benign according to our data. Variant chr8-96143132-CCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 364012.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDF6	NM_001001557.4	c.*1429_*1430delAG		3_prime_UTR_variant	2/2	ENST00000287020.7	NP_001001557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF6	ENST00000287020	c.*1429_*1430delAG		3_prime_UTR_variant	2/2	1	NM_001001557.4	ENSP00000287020.4

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5559 AN: 152162 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0323

Gnomad OTH AF: 0.0359

GnomAD4 exome AF: 0.0313 AC: 2 AN: 64 Hom.: 0 AF XY: 0.0455 AC XY: 2 AN XY: 44

Gnomad4 FIN exome AF: 0.0263

Gnomad4 NFE exome AF: 0.0500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0365 AC: 5559 AN: 152280 Hom.: 121 Cov.: 32 AF XY: 0.0337 AC XY: 2511 AN XY: 74474

Gnomad4 AFR AF: 0.0600

Gnomad4 AMR AF: 0.0261

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.0323

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0361 Hom.: 20

Bravo AF: 0.0393

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Klippel-Feil syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs139734303; hg19: chr8-97155360;