2-163610050-T-G

Variant names:

• chr2-163610050-T-G
• NM_018086.4:c.1782A>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_018086.4(FIGN):​c.1782A>C​(p.Gln594His) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FIGN NM_018086.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FIGN	NM_018086.4	c.1782A>C	p.Gln594His	missense_variant	Exon 3 of 3	ENST00000333129.4	NP_060556.2
FIGN	NM_001321825.2	c.1749A>C	p.Gln583His	missense_variant	Exon 2 of 2		NP_001308754.1
FIGN	XM_047444863.1	c.1860A>C	p.Gln620His	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.1782A>C	p.Gln594His	missense_variant	Exon 3 of 3	1	NM_018086.4	ENSP00000333836.3
FIGN	ENST00000409634.5	c.26-16254A>C		intron_variant	Intron 2 of 2	5		ENSP00000386768.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1782A>C (p.Q594H) alteration is located in exon 3 (coding exon 2) of the FIGN gene. This alteration results from a A to C substitution at nucleotide position 1782, causing the glutamine (Q) at amino acid position 594 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	0.10
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	0.38	N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.63	N
REVEL	Uncertain	0.55
Sift	Benign	0.15	T
Sift4G	Benign	0.40	T
Polyphen		0.071	B
Vest4		0.57
MutPred		0.84		Loss of stability (P = 0.0786);
MVP		0.66
MPC		0.22
ClinPred		0.26	T
GERP RS		0.62
Varity_R		0.19
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-164466560;