Variant chr2-152619514-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_052905.4(FMNL2):c.1633A>G(p.Asn545Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,397,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FMNL2
NM_052905.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.08

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, FMNL2

BP4

Computational evidence support a benign effect (MetaRNN=0.28894734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMNL2	NM_052905.4 linkuse as main transcript	c.1633A>G	p.Asn545Asp	missense_variant	15/26	ENST00000288670.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMNL2	ENST00000288670.14 linkuse as main transcript	c.1633A>G	p.Asn545Asp	missense_variant	15/26	1	NM_052905.4	P1	Q96PY5-3
FMNL2	ENST00000475377.3 linkuse as main transcript	c.1633A>G	p.Asn545Asp	missense_variant	15/28	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000649

AC:

AN:

154034

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

81724

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000172

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1397708

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

689326

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.1633A>G (p.N545D) alteration is located in exon 15 (coding exon 15) of the FMNL2 gene. This alteration results from a A to G substitution at nucleotide position 1633, causing the asparagine (N) at amino acid position 545 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Benign

-0.12

Eigen_PC

Benign

0.090

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.79

M_CAP

Benign

0.017

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.88

REVEL

Benign

0.081

Sift

Benign

0.23

Sift4G

Benign

0.63

Polyphen

0.14

Vest4

0.56

MutPred

0.18

Gain of loop (P = 0.024);

MVP

0.38

MPC

0.79

ClinPred

0.78

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.080

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