rs759951553

Variant names:

• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-C
• rs759951553
• NM_005811.5:c.93_116delGGCGGCGGCGGCGGCGGCGGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-C
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG
• chr12-55743400-CGCGGCGGCGGCGGCGGCGGCGGCG-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_005811.5(GDF11):​c.93_116delGGCGGCGGCGGCGGCGGCGGCGGC​(p.Ala32_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 0.00000118 in 847,110 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: GDF11 NM_005811.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• vertebral hypersegmentation and orofacial anomalies

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_005811.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005811.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF11	NM_005811.5	MANE Select	c.93_116delGGCGGCGGCGGCGGCGGCGGCGGC	p.Ala32_Ala39del	disruptive_inframe_deletion	Exon 1 of 3	NP_005802.1	O95390

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDF11	ENST00000257868.10	TSL:1 MANE Select	c.93_116delGGCGGCGGCGGCGGCGGCGGCGGC	p.Ala32_Ala39del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000257868.5	O95390
	GDF11	ENST00000546799.1	TSL:1	c.9_32delGGCGGCGGCGGCGGCGGCGGCGGC	p.Ala4_Ala11del	disruptive_inframe_deletion	Exon 1 of 4	ENSP00000448390.1	H0YI30

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000118 AC: 1 AN: 847110 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 393726

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15978

American (AMR) AF: 0.00 AC: 0 AN: 1414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5408

East Asian (EAS) AF: 0.00 AC: 0 AN: 4100

South Asian (SAS) AF: 0.00 AC: 0 AN: 17416

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1684

European-Non Finnish (NFE) AF: 0.00000130 AC: 1 AN: 771830

Other (OTH) AF: 0.00 AC: 0 AN: 27990

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.3

Splicing

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

Other links and lift over

dbSNP: rs759951553; hg19: chr12-56137184;