2-163609907-C-T

Variant names:

• chr2-163609907-C-T
• rs1691196521
• NM_018086.4:c.1925G>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_018086.4(FIGN):​c.1925G>A​(p.Arg642Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FIGN NM_018086.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGN	NM_018086.4	c.1925G>A	p.Arg642Lys	missense_variant	Exon 3 of 3	ENST00000333129.4	NP_060556.2
FIGN	NM_001321825.2	c.1892G>A	p.Arg631Lys	missense_variant	Exon 2 of 2		NP_001308754.1
FIGN	XM_047444863.1	c.2003G>A	p.Arg668Lys	missense_variant	Exon 3 of 3		XP_047300819.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FIGN	ENST00000333129.4	c.1925G>A	p.Arg642Lys	missense_variant	Exon 3 of 3	1	NM_018086.4	ENSP00000333836.3
FIGN	ENST00000409634.5	c.26-16111G>A		intron_variant	Intron 2 of 2	5		ENSP00000386768.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1925G>A (p.R642K) 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 1925, causing the arginine (R) at amino acid position 642 to be replaced by a lysine (K). 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	0.28
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.90	D
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.1	M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.9	D
REVEL	Pathogenic	0.90
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.034	D
Polyphen		0.99	D
Vest4		0.85
MutPred		0.91		Gain of methylation at R642 (P = 0.0053);
MVP		0.91
MPC		0.75
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.80
gMVP		0.72

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

Other links and lift over

dbSNP: rs1691196521; hg19: chr2-164466417;