chr2-215361610-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP2PP3PP5
The NM_212482.4(FN1):c.7379T>C(p.Ile2460Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,611,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
FN1
NM_212482.4 missense
NM_212482.4 missense
Scores
9
6
2
Clinical Significance
Conservation
PhyloP100: 5.80
Genes affected
FN1 (HGNC:3778): (fibronectin 1) This gene encodes fibronectin, a glycoprotein present in a soluble dimeric form in plasma, and in a dimeric or multimeric form at the cell surface and in extracellular matrix. The encoded preproprotein is proteolytically processed to generate the mature protein. Fibronectin is involved in cell adhesion and migration processes including embryogenesis, wound healing, blood coagulation, host defense, and metastasis. The gene has three regions subject to alternative splicing, with the potential to produce 20 different transcript variants, at least one of which encodes an isoform that undergoes proteolytic processing. The full-length nature of some variants has not been determined. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, FN1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.779
PP5
?
Variant 2-215361610-A-G is Pathogenic according to our data. Variant chr2-215361610-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1344882.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FN1 | NM_212482.4 | c.7379T>C | p.Ile2460Thr | missense_variant | 46/46 | ENST00000354785.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FN1 | ENST00000354785.11 | c.7379T>C | p.Ile2460Thr | missense_variant | 46/46 | 1 | NM_212482.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1459112Hom.: 0 Cov.: 28 AF XY: 0.0000110 AC XY: 8AN XY: 726158
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Nephrotic syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Yale Center for Mendelian Genomics, Yale University | Nov 10, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N;D;N;N;N;N;D;N;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D;D
Polyphen
D;B;P;D;B;D;.;D;D;D;.
Vest4
MutPred
0.51
.;.;.;.;.;Gain of disorder (P = 0.0039);.;.;.;.;.;
MVP
MPC
0.52
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at