Genetic Variant FMNL2:p.Leu110Val (chr2-152549066-C-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_052905.4(FMNL2):c.328C>G(p.Leu110Val) variant causes a missense change. The variant allele was found at a frequency of 0.00165 in 1,610,452 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

FMNL2
NM_052905.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.49

Publications

9 publications found

Variant links:

Genes affected

FMNL2 (HGNC:18267): (formin like 2) This gene encodes a formin-related protein. Formin-related proteins have been implicated in morphogenesis, cytokinesis, and cell polarity. Alternatively spliced transcript variants encoding different isoforms have been described but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

FMNL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06383386).

BP6

Variant 2-152549066-C-G is Benign according to our data. Variant chr2-152549066-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 791523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMNL2	NM_052905.4 link	c.328C>G	p.Leu110Val	missense_variant	Exon 4 of 26	ENST00000288670.14	NP_443137.2	Q96PY5-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMNL2	ENST00000288670.14 link	c.328C>G	p.Leu110Val	missense_variant	Exon 4 of 26	1	NM_052905.4	ENSP00000288670.9		Q96PY5-3

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

243

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00159

AC:

388

AN:

243758

AF XY:

0.00171

show subpopulations

Gnomad AFR exome

AF:

0.000397

Gnomad AMR exome

AF:

0.000445

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00201

Gnomad NFE exome

AF:

0.00247

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.00166

AC:

2420

AN:

1458176

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1234

AN XY:

725012

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33408

American (AMR)

AF:

0.000724

AC:

AN:

44180

Ashkenazi Jewish (ASJ)

AF:

0.000115

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39538

South Asian (SAS)

AF:

0.00173

AC:

147

AN:

85142

European-Finnish (FIN)

AF:

0.00242

AC:

129

AN:

53300

Middle Eastern (MID)

AF:

0.00296

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00180

AC:

2001

AN:

1110524

Other (OTH)

AF:

0.00139

AC:

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

110

220

330

440

550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00160

AC:

243

AN:

152276

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000409

AC:

AN:

41562

American (AMR)

AF:

0.00170

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00253

AC:

172

AN:

68018

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00157

Hom.:

Bravo

AF:

0.00152

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000276

AC:

ESP6500EA

AF:

0.00209

AC:

ExAC

AF:

0.00174

AC:

210

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.45

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

1.0

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.064

MetaSVM

Pathogenic

0.90

MutationAssessor

Pathogenic

3.5

PhyloP100

4.5

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.3

REVEL

Pathogenic

0.85

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.97

Vest4

0.75

MVP

0.89

MPC

0.94

ClinPred

0.11

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.65

Mutation Taster

=18/82

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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2-152549066-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over