Variant 12-55743400-CGCGGCGGCGGCGGCGGCG-CGCGGCGGCG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BP6BS2

The NM_005811.5(GDF11):c.108_116delGGCGGCGGC(p.Ala37_Ala39del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 992,838 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0030 ( 1 hom. )

Consequence

GDF11
NM_005811.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.25

Variant links:

Genes affected

GDF11 (HGNC:4216): (growth differentiation factor 11) 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 plays a role in the development of the nervous and other organ systems, and may regulate aging. [provided by RefSeq, Aug 2016]

GDF11 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_005811.5

BP6

Variant 12-55743400-CGCGGCGGCG-C is Benign according to our data. Variant chr12-55743400-CGCGGCGGCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 3034015.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 255 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF11	NM_005811.5 link	c.108_116delGGCGGCGGC	p.Ala37_Ala39del	disruptive_inframe_deletion	Exon 1 of 3	ENST00000257868.10	NP_005802.1	O95390A0A024RB20
GDF11	XM_006719194.4 link	c.108_116delGGCGGCGGC	p.Ala37_Ala39del	disruptive_inframe_deletion	Exon 1 of 4		XP_006719257.1	O95390A0A024RB20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF11	ENST00000257868.10 link	c.108_116delGGCGGCGGC	p.Ala37_Ala39del	disruptive_inframe_deletion	Exon 1 of 3	1	NM_005811.5	ENSP00000257868.5		O95390
GDF11	ENST00000546799.1 link	c.24_32delGGCGGCGGC	p.Ala9_Ala11del	disruptive_inframe_deletion	Exon 1 of 4	1		ENSP00000448390.1		H0YI30

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

254

AN:

145656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000813

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000543

Gnomad ASJ

AF:

0.000296

Gnomad EAS

AF:

0.00358

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00120

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00273

Gnomad OTH

AF:

0.00248

GnomAD4 exome

AF:

0.00296

AC:

2508

AN:

847082

Hom.:

AF XY:

0.00304

AC XY:

1197

AN XY:

393710

show subpopulations

Gnomad4 AFR exome

AF:

0.000563

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00463

Gnomad4 SAS exome

AF:

0.000172

Gnomad4 FIN exome

AF:

0.0101

Gnomad4 NFE exome

AF:

0.00313

Gnomad4 OTH exome

AF:

0.00168

GnomAD4 genome

AF:

0.00175

AC:

255

AN:

145756

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

119

AN XY:

70870

show subpopulations

Gnomad4 AFR

AF:

0.000811

Gnomad4 AMR

AF:

0.000543

Gnomad4 ASJ

AF:

0.000296

Gnomad4 EAS

AF:

0.00359

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00120

Gnomad4 NFE

AF:

0.00273

Gnomad4 OTH

AF:

0.00295

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GDF11-related disorder

Benign:1

May 17, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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