12-55743400-C-CGCGGCG
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2
The NM_005811.5(GDF11):c.111_116dupGGCGGC(p.Ala38_Ala39dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000515 in 992,846 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0015 ( 2 hom., cov: 30)
Exomes 𝑓: 0.00035 ( 0 hom. )
Consequence
GDF11
NM_005811.5 disruptive_inframe_insertion
NM_005811.5 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.392
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 anomaliesInheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -7 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_005811.5
BP6
Variant 12-55743400-C-CGCGGCG is Benign according to our data. Variant chr12-55743400-C-CGCGGCG is described in ClinVar as Likely_benign. ClinVar VariationId is 3910969.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 215 Unknown,AD gene.
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.111_116dupGGCGGC | p.Ala38_Ala39dup | disruptive_inframe_insertion | 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.111_116dupGGCGGC | p.Ala38_Ala39dup | disruptive_inframe_insertion | Exon 1 of 3 | ENSP00000257868.5 | O95390 | |
| GDF11 | ENST00000546799.1 | TSL:1 | c.27_32dupGGCGGC | p.Ala10_Ala11dup | disruptive_inframe_insertion | Exon 1 of 4 | ENSP00000448390.1 | H0YI30 |
Frequencies
GnomAD3 genomes 0.00148 AC: 215AN: 145656Hom.: 2 Cov.: 30 show subpopulations
GnomAD3 genomes
AF:
AC:
215
AN:
145656
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000349 AC: 296AN: 847090Hom.: 0 Cov.: 28 AF XY: 0.000363 AC XY: 143AN XY: 393716 show subpopulations
GnomAD4 exome
AF:
AC:
296
AN:
847090
Hom.:
Cov.:
28
AF XY:
AC XY:
143
AN XY:
393716
show subpopulations
African (AFR)
AF:
AC:
81
AN:
15978
American (AMR)
AF:
AC:
1
AN:
1414
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
5408
East Asian (EAS)
AF:
AC:
3
AN:
4098
South Asian (SAS)
AF:
AC:
6
AN:
17416
European-Finnish (FIN)
AF:
AC:
0
AN:
1290
Middle Eastern (MID)
AF:
AC:
3
AN:
1684
European-Non Finnish (NFE)
AF:
AC:
186
AN:
771812
Other (OTH)
AF:
AC:
16
AN:
27990
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.421
Heterozygous variant carriers
0
12
24
36
48
60
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.00148 AC: 215AN: 145756Hom.: 2 Cov.: 30 AF XY: 0.00168 AC XY: 119AN XY: 70870 show subpopulations
GnomAD4 genome
AF:
AC:
215
AN:
145756
Hom.:
Cov.:
30
AF XY:
AC XY:
119
AN XY:
70870
show subpopulations
African (AFR)
AF:
AC:
175
AN:
40696
American (AMR)
AF:
AC:
4
AN:
14742
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3384
East Asian (EAS)
AF:
AC:
9
AN:
5018
South Asian (SAS)
AF:
AC:
2
AN:
4770
European-Finnish (FIN)
AF:
AC:
0
AN:
8316
Middle Eastern (MID)
AF:
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
AC:
24
AN:
65598
Other (OTH)
AF:
AC:
1
AN:
2036
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
8
16
25
33
41
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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