2-163609781-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018086.4(FIGN):​c.2051G>A​(p.Arg684His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,116 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

FIGN
NM_018086.4 missense

Scores

8
5
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
FIGN (HGNC:13285): (fidgetin, microtubule severing factor) Predicted to enable microtubule-severing ATPase activity. Predicted to be involved in cytoplasmic microtubule organization. Predicted to act upstream of or within locomotory behavior. Predicted to be located in nuclear matrix. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FIGNNM_018086.4 linkc.2051G>A p.Arg684His missense_variant Exon 3 of 3 ENST00000333129.4 NP_060556.2 Q5HY92
FIGNNM_001321825.2 linkc.2018G>A p.Arg673His missense_variant Exon 2 of 2 NP_001308754.1
FIGNXM_047444863.1 linkc.2129G>A p.Arg710His missense_variant Exon 3 of 3 XP_047300819.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FIGNENST00000333129.4 linkc.2051G>A p.Arg684His missense_variant Exon 3 of 3 1 NM_018086.4 ENSP00000333836.3 Q5HY92
FIGNENST00000409634.5 linkc.26-15985G>A intron_variant Intron 2 of 2 5 ENSP00000386768.1 B8ZZS6

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152146
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000281
AC:
7
AN:
249094
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135122
show subpopulations
Gnomad AFR exome
AF:
0.000194
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000558
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461852
Hom.:
0
Cov.:
37
AF XY:
0.0000316
AC XY:
23
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000812
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152264
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000793
ESP6500AA
AF:
0.000242
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000331
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2051G>A (p.R684H) alteration is located in exon 3 (coding exon 2) of the FIGN gene. This alteration results from a G to A substitution at nucleotide position 2051, causing the arginine (R) at amino acid position 684 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.43
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.65
D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Uncertain
2.3
M
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-1.8
N
REVEL
Pathogenic
0.70
Sift
Benign
0.22
T
Sift4G
Benign
0.21
T
Polyphen
0.99
D
Vest4
0.69
MVP
0.72
MPC
0.31
ClinPred
0.19
T
GERP RS
5.9
Varity_R
0.14
gMVP
0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs375256647; hg19: chr2-164466291; COSMIC: COSV60765585; COSMIC: COSV60765585; API