1-240092472-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_020066.5(FMN2):c.363C>T(p.Leu121=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,609,000 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (62 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (76 hom.)
• Consequence: FMN2 NM_020066.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.537

Genes affected

FMN2 (HGNC:14074): (formin 2) This gene is a member of the formin homology protein family. The encoded protein is thought to have essential roles in organization of the actin cytoskeleton and in cell polarity. This protein mediates the formation of an actin mesh that positions the spindle during oogenesis and also regulates the formation of actin filaments in the nucleus. This protein also forms a perinuclear actin/focal-adhesion system that regulates the shape and position of the nucleus during cell migration. Mutations in this gene have been associated with infertility and also with an autosomal recessive form of intellectual disability (MRT47). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 1-240092472-C-T is Benign according to our data. Variant chr1-240092472-C-T is described in ClinVar as [Benign]. Clinvar id is 777107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.537 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN2	NM_020066.5	c.363C>T	p.Leu121=	synonymous_variant	1/18	ENST00000319653.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN2	ENST00000319653.14	c.363C>T	p.Leu121=	synonymous_variant	1/18	5	NM_020066.5	P1
FMN2	ENST00000447095.5	c.-87+24399C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2319 AN: 152044 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.0533

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0115

GnomAD3 exomes AF: 0.00369 AC: 871 AN: 236152 Hom.: 20 AF XY: 0.00275 AC XY: 354 AN XY: 128532

Gnomad AFR exome AF: 0.0543

Gnomad AMR exome AF: 0.00240

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000169

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000569

Gnomad OTH exome AF: 0.00172

GnomAD4 exome AF: 0.00159 AC: 2319 AN: 1456838 Hom.: 76 Cov.: 89 AF XY: 0.00132 AC XY: 954 AN XY: 724352

Gnomad4 AFR exome AF: 0.0572

Gnomad4 AMR exome AF: 0.00286

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000152

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000442

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome AF: 0.0153 AC: 2324 AN: 152162 Hom.: 62 Cov.: 33 AF XY: 0.0149 AC XY: 1109 AN XY: 74392

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00705 Hom.: 13

Bravo AF: 0.0172

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	14
Dann	Benign	0.94

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: rs112904598; hg19: chr1-240255772; COSMIC: COSV60432109;