12-51821010-C-G

Variant names:

• chr12-51821010-C-G
• rs1939165408
• NM_001384995.1:c.1404G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001384995.1(FIGNL2):​c.1404G>C​(p.Glu468Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: FIGNL2 NM_001384995.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.181
• Publications: 0 publications found

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]

ENSG00000260473 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384995.1. 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
	FIGNL2	NM_001384995.1	MANE Select	c.1404G>C	p.Glu468Asp	missense	Exon 2 of 2	NP_001371924.1	A6NMB9
	FIGNL2	NM_001013690.5		c.1404G>C	p.Glu468Asp	missense	Exon 2 of 2	NP_001013712.4	A6NMB9
	FIGNL2	NM_001384996.1		c.1404G>C	p.Glu468Asp	missense	Exon 3 of 3	NP_001371925.1	A6NMB9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FIGNL2	ENST00000618634.3	TSL:5 MANE Select	c.1404G>C	p.Glu468Asp	missense	Exon 2 of 2	ENSP00000491257.1	A6NMB9
	FIGNL2	ENST00000938505.1		c.1404G>C	p.Glu468Asp	missense	Exon 2 of 2	ENSP00000608564.1
	FIGNL2	ENST00000948593.1		c.1404G>C	p.Glu468Asp	missense	Exon 2 of 2	ENSP00000618652.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1030388 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 487230

African (AFR) AF: 0.00 AC: 0 AN: 20840

American (AMR) AF: 0.00 AC: 0 AN: 6644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11724

East Asian (EAS) AF: 0.00 AC: 0 AN: 21074

South Asian (SAS) AF: 0.00 AC: 0 AN: 19182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2634

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 889538

Other (OTH) AF: 0.00 AC: 0 AN: 39620

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Uncertain	0.49	T
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.47	T
MetaRNN	Uncertain	0.68	D
MutationAssessor	Benign	1.6	L
PhyloP100		0.18
PrimateAI	Pathogenic	0.92	D
Polyphen		0.97	D
GERP RS		-0.051
Varity_R		0.11
gMVP		0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1939165408; hg19: chr12-52214794;