Genetic Variant NM_001384995.1:c.1343A>G (chr12-51821071-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001384995.1(FIGNL2):c.1343A>G(p.Gln448Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00015 in 1,283,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

FIGNL2
NM_001384995.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.37

Variant links:

Genes affected

FIGNL2 (HGNC:13287): (fidgetin like 2) Predicted to enable microtubule-severing ATPase activity. Predicted to be involved in cytoplasmic microtubule organization. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FIGNL2 links:

ENSG00000260473 (HGNC:):

ENSG00000260473 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4109315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGNL2	NM_001384995.1 link	c.1343A>G	p.Gln448Arg	missense_variant	Exon 2 of 2	ENST00000618634.3	NP_001371924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGNL2	ENST00000618634.3 link	c.1343A>G	p.Gln448Arg	missense_variant	Exon 2 of 2	5	NM_001384995.1	ENSP00000491257.1		A6NMB9
ENSG00000260473	ENST00000637934.1 link	n.177-2374T>C		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes

AF:

0.000200

AC:

AN:

150218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000972

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000861

Gnomad ASJ

AF:

0.000579

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0000889

Gnomad OTH

AF:

0.000485

GnomAD4 exome

AF:

0.000143

AC:

162

AN:

1133216

Hom.:

Cov.:

AF XY:

0.000160

AC XY:

AN XY:

544178

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.000847

Gnomad4 ASJ exome

AF:

0.00108

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000838

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000798

Gnomad4 OTH exome

AF:

0.000462

GnomAD4 genome

AF:

0.000200

AC:

AN:

150326

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

AN XY:

73472

show subpopulations

Gnomad4 AFR

AF:

0.0000969

Gnomad4 AMR

AF:

0.000860

Gnomad4 ASJ

AF:

0.000579

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000890

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000283

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1343A>G (p.Q448R) alteration is located in exon 2 (coding exon 1) of the FIGNL2 gene. This alteration results from a A to G substitution at nucleotide position 1343, causing the glutamine (Q) at amino acid position 448 to be replaced by an arginine (R). 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

0.23

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Uncertain

0.63

D;D

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.57

.;T

MetaRNN

Benign

0.41

T;T

MutationAssessor

Benign

1.2

L;L

PrimateAI

Pathogenic

0.93

Polyphen

0.013

B;B

GERP RS

2.8

Varity_R

0.066

gMVP

0.70

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over