chr2-163610508-T-G

Variant names:

• chr2-163610508-T-G
• rs186030983
• NM_018086.4:c.1324A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018086.4(FIGN):​c.1324A>C​(p.Met442Leu) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FIGN NM_018086.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045672327).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018086.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIGN	NM_018086.4	MANE Select	c.1324A>C	p.Met442Leu	missense	Exon 3 of 3	NP_060556.2	Q5HY92
	FIGN	NM_001321825.2		c.1291A>C	p.Met431Leu	missense	Exon 2 of 2	NP_001308754.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIGN	ENST00000333129.4	TSL:1 MANE Select	c.1324A>C	p.Met442Leu	missense	Exon 3 of 3	ENSP00000333836.3	Q5HY92
	FIGN	ENST00000879555.1		c.1324A>C	p.Met442Leu	missense	Exon 3 of 3	ENSP00000549614.1
	FIGN	ENST00000409634.5	TSL:5	c.26-16712A>C		intron	N/A	ENSP00000386768.1	B8ZZS6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249288 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.75
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	-0.46	N
PhyloP100		2.9
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.25
Sift	Benign	0.74	T
Sift4G	Benign	0.98	T
Polyphen		0.0020	B
Vest4		0.17
MutPred		0.17		Loss of helix (P = 0.0626)
MVP		0.22
MPC		0.20
ClinPred		0.14	T
GERP RS		3.5
Varity_R		0.058
gMVP		0.32
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs186030983; hg19: chr2-164467018;