Variant chr2-152619149-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4_StrongBP6_ModerateBS2

The NM_052905.4(FMNL2):c.1618C>T(p.Pro540Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00467 in 1,559,378 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 16 hom. )

Consequence

FMNL2
NM_052905.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.184

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PP2

Missense variant where missense usually causes diseases, FMNL2

BP4

Computational evidence support a benign effect (MetaRNN=0.0044614077).

BP6

Variant 2-152619149-C-T is Benign according to our data. Variant chr2-152619149-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 776344.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMNL2	NM_052905.4 linkuse as main transcript	c.1618C>T	p.Pro540Ser	missense_variant	14/26	ENST00000288670.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMNL2	ENST00000288670.14 linkuse as main transcript	c.1618C>T	p.Pro540Ser	missense_variant	14/26	1	NM_052905.4	P1	Q96PY5-3
FMNL2	ENST00000475377.3 linkuse as main transcript	c.1618C>T	p.Pro540Ser	missense_variant	14/28	5

Frequencies

GnomAD3 genomes

AF:

0.00378

AC:

576

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00638

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00479

AC:

979

AN:

204370

Hom.:

AF XY:

0.00482

AC XY:

535

AN XY:

111070

show subpopulations

Gnomad AFR exome

AF:

0.00108

Gnomad AMR exome

AF:

0.00250

Gnomad ASJ exome

AF:

0.00317

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00433

Gnomad NFE exome

AF:

0.00789

Gnomad OTH exome

AF:

0.00467

GnomAD4 exome

AF:

0.00477

AC:

6714

AN:

1407062

Hom.:

Cov.:

AF XY:

0.00476

AC XY:

3311

AN XY:

695800

show subpopulations

Gnomad4 AFR exome

AF:

0.000841

Gnomad4 AMR exome

AF:

0.00247

Gnomad4 ASJ exome

AF:

0.00318

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000294

Gnomad4 FIN exome

AF:

0.00445

Gnomad4 NFE exome

AF:

0.00553

Gnomad4 OTH exome

AF:

0.00445

GnomAD4 genome

AF:

0.00378

AC:

576

AN:

152316

Hom.:

Cov.:

AF XY:

0.00380

AC XY:

283

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00638

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00584

Hom.:

Bravo

AF:

0.00328

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00103

AC:

ESP6500EA

AF:

0.00411

AC:

ExAC

AF:

0.00517

AC:

625

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.75

M_CAP

Benign

0.027

MetaRNN

Benign

0.0045

MetaSVM

Benign

-0.70

MutationAssessor

Benign

-0.060

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.82

REVEL

Benign

0.23

Sift

Benign

0.50

Sift4G

Benign

0.24

Polyphen

0.0

Vest4

0.061

MVP

0.25

MPC

0.35

ClinPred

0.0087

GERP RS

0.99

gMVP

0.065

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over