2-163609800-A-C

Variant names:

• chr2-163609800-A-C
• rs1691192911
• NM_018086.4:c.2032T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018086.4(FIGN):​c.2032T>G​(p.Phe678Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FIGN NM_018086.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09369311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGN	NM_018086.4	c.2032T>G	p.Phe678Val	missense_variant	Exon 3 of 3	ENST00000333129.4	NP_060556.2
FIGN	NM_001321825.2	c.1999T>G	p.Phe667Val	missense_variant	Exon 2 of 2		NP_001308754.1
FIGN	XM_047444863.1	c.2110T>G	p.Phe704Val	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.2032T>G	p.Phe678Val	missense_variant	Exon 3 of 3	1	NM_018086.4	ENSP00000333836.3
FIGN	ENST00000409634.5	c.26-16004T>G		intron_variant	Intron 2 of 2	5		ENSP00000386768.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461856 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2032T>G (p.F678V) alteration is located in exon 3 (coding exon 2) of the FIGN gene. This alteration results from a T to G substitution at nucleotide position 2032, causing the phenylalanine (F) at amino acid position 678 to be replaced by a valine (V). 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	0.063
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.064
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.094	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	-0.070	N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.25
Sift	Benign	0.40	T
Sift4G	Benign	0.22	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.53		Loss of ubiquitination at K676 (P = 0.0801);
MVP		0.093
MPC		0.28
ClinPred		0.82	D
GERP RS		4.6
Varity_R		0.052
gMVP		0.56

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: rs1691192911; hg19: chr2-164466310;