Variant rs62516290 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001001557.4(GDF6):c.406+28C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 1,612,804 control chromosomes in the GnomAD database, including 5,711 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 397 hom., cov: 33)

Exomes 𝑓: 0.080 ( 5314 hom. )

Consequence

GDF6
NM_001001557.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.20

Variant links:

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]

GDF6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 8-96160259-G-T is Benign according to our data. Variant chr8-96160259-G-T is described in ClinVar as [Benign]. Clinvar id is 256848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-96160259-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDF6	NM_001001557.4 linkuse as main transcript	c.406+28C>A		intron_variant		ENST00000287020.7	NP_001001557.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDF6	ENST00000287020.7 linkuse as main transcript	c.406+28C>A		intron_variant		1	NM_001001557.4	ENSP00000287020	P1

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

9634

AN:

152200

Hom.:

396

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0274

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.0605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0487

Gnomad MID

AF:

0.102

Gnomad NFE

AF:

0.0936

Gnomad OTH

AF:

0.0737

GnomAD3 exomes

AF:

0.0624

AC:

15589

AN:

249932

Hom.:

660

AF XY:

0.0629

AC XY:

8511

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.0262

Gnomad AMR exome

AF:

0.0564

Gnomad ASJ exome

AF:

0.0659

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0163

Gnomad FIN exome

AF:

0.0528

Gnomad NFE exome

AF:

0.0923

Gnomad OTH exome

AF:

0.0845

GnomAD4 exome

AF:

0.0801

AC:

116965

AN:

1460486

Hom.:

5314

Cov.:

AF XY:

0.0787

AC XY:

57183

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.0232

Gnomad4 AMR exome

AF:

0.0586

Gnomad4 ASJ exome

AF:

0.0627

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0160

Gnomad4 FIN exome

AF:

0.0553

Gnomad4 NFE exome

AF:

0.0926

Gnomad4 OTH exome

AF:

0.0727

GnomAD4 genome

AF:

0.0632

AC:

9633

AN:

152318

Hom.:

397

Cov.:

AF XY:

0.0601

AC XY:

4477

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0273

Gnomad4 AMR

AF:

0.0695

Gnomad4 ASJ

AF:

0.0605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.0487

Gnomad4 NFE

AF:

0.0937

Gnomad4 OTH

AF:

0.0729

Alfa

AF:

0.0794

Hom.:

Bravo

AF:

0.0647

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 22, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.9

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over