5-128335243-G-C
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7
The ENST00000262464.9(FBN2):c.3900C>G(p.Thr1300Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T1300T) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
FBN2
ENST00000262464.9 synonymous
ENST00000262464.9 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.36
Publications
0 publications found
Genes affected
FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]
FBN2 Gene-Disease associations (from GenCC):
- congenital contractural arachnodactylyInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
- carpal tunnel syndromeInheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox
- familial thoracic aortic aneurysm and aortic dissectionInheritance: AD Classification: LIMITED Submitted by: ClinGen
- macular degeneration, early-onsetInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP7
Synonymous conserved (PhyloP=1.36 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000262464.9. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FBN2 | NM_001999.4 | MANE Select | c.3900C>G | p.Thr1300Thr | synonymous | Exon 30 of 65 | NP_001990.2 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FBN2 | ENST00000262464.9 | TSL:1 MANE Select | c.3900C>G | p.Thr1300Thr | synonymous | Exon 30 of 65 | ENSP00000262464.4 | ||
| FBN2 | ENST00000508989.5 | TSL:2 | c.3801C>G | p.Thr1267Thr | synonymous | Exon 29 of 33 | ENSP00000425596.1 | ||
| FBN2 | ENST00000507835.5 | TSL:5 | n.687C>G | non_coding_transcript_exon | Exon 5 of 9 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152052
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
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Gnomad NFE
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Gnomad OTH
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GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251294 AF XY: 0.00000736 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
251294
AF XY:
Gnomad AFR exome
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Gnomad ASJ exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461830Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727224 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1461830
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
727224
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26134
East Asian (EAS)
AF:
AC:
2
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111956
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
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0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00000658 AC: 1AN: 152052Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74250 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152052
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
74250
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41390
American (AMR)
AF:
AC:
0
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5186
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10582
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
1
AN:
68012
Other (OTH)
AF:
AC:
0
AN:
2082
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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