rs756747736

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001999.4(FBN2):​c.7497G>T​(p.Pro2499Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,502 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. P2499P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FBN2
NM_001999.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.22

Publications

0 publications found
Variant links:
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 arachnodactyly
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
  • carpal tunnel syndrome
    Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox
  • familial thoracic aortic aneurysm and aortic dissection
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • macular degeneration, early-onset
    Inheritance: 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 -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP7
Synonymous conserved (PhyloP=-5.22 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FBN2NM_001999.4 linkc.7497G>T p.Pro2499Pro synonymous_variant Exon 59 of 65 ENST00000262464.9 NP_001990.2 P35556-1
FBN2XM_017009228.3 linkc.7344G>T p.Pro2448Pro synonymous_variant Exon 58 of 64 XP_016864717.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FBN2ENST00000262464.9 linkc.7497G>T p.Pro2499Pro synonymous_variant Exon 59 of 65 1 NM_001999.4 ENSP00000262464.4 P35556-1
FBN2ENST00000703783.1 linkn.4281G>T non_coding_transcript_exon_variant Exon 34 of 38

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461502
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727078
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33462
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26116
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39672
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1111724
Other (OTH)
AF:
0.00
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.61
CADD
Benign
0.64
DANN
Benign
0.45
PhyloP100
-5.2

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs756747736; hg19: chr5-127611827; API