12-55743400-CGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant names:

• chr12-55743400-C-CGCGGCGGCGGCGGCGGCGGCG
• rs759951553
• NM_005811.5:c.96_116dupGGCGGCGGCGGCGGCGGCGGC

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP3

The NM_005811.5(GDF11):​c.96_116dupGGCGGCGGCGGCGGCGGCGGC​(p.Ala33_Ala39dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GDF11 NM_005811.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_005811.5

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDF11	NM_005811.5	c.96_116dupGGCGGCGGCGGCGGCGGCGGC	p.Ala33_Ala39dup	disruptive_inframe_insertion	Exon 1 of 3	ENST00000257868.10	NP_005802.1
GDF11	XM_006719194.4	c.96_116dupGGCGGCGGCGGCGGCGGCGGC	p.Ala33_Ala39dup	disruptive_inframe_insertion	Exon 1 of 4		XP_006719257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDF11	ENST00000257868.10	c.96_116dupGGCGGCGGCGGCGGCGGCGGC	p.Ala33_Ala39dup	disruptive_inframe_insertion	Exon 1 of 3	1	NM_005811.5	ENSP00000257868.5
GDF11	ENST00000546799.1	c.12_32dupGGCGGCGGCGGCGGCGGCGGC	p.Ala5_Ala11dup	disruptive_inframe_insertion	Exon 1 of 4	1		ENSP00000448390.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000354 AC: 3 AN: 847110 Hom.: 0 Cov.: 28 AF XY: 0.00000254 AC XY: 1 AN XY: 393726

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000389

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs759951553; hg19: chr12-56137184;