Variant 2-28412059-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005253.4(FOSL2):c.592C>T(p.Arg198Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,607,526 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

FOSL2
NM_005253.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

Variant links:

Genes affected

FOSL2 (HGNC:3798): (FOS like 2, AP-1 transcription factor subunit) The Fos gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation. [provided by RefSeq, Jul 2014]

FOSL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20964971).

BS2

High AC in GnomAdExome4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOSL2	NM_005253.4 link	c.592C>T	p.Arg198Cys	missense_variant	4/4	ENST00000264716.9	NP_005244.1	P15408-1Q9H5M2
FOSL2	XM_006711976.4 link	c.643C>T	p.Arg215Cys	missense_variant	4/4		XP_006712039.1
FOSL2	XM_006711977.4 link	c.526C>T	p.Arg176Cys	missense_variant	4/4		XP_006712040.1
FOSL2	XM_005264231.5 link	c.*77C>T		3_prime_UTR_variant	5/5		XP_005264288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FOSL2	ENST00000264716.9 link	c.592C>T	p.Arg198Cys	missense_variant	4/4	1	NM_005253.4	ENSP00000264716.4	P15408-1
FOSL2	ENST00000379619.5 link	c.568C>T	p.Arg190Cys	missense_variant	4/4	1		ENSP00000368939.1	P15408-2
FOSL2	ENST00000436647.1 link	c.475C>T	p.Arg159Cys	missense_variant	4/4	2		ENSP00000396497.1	C9JCN8

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151338

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000410

AC:

AN:

243928

Hom.:

AF XY:

0.0000528

AC XY:

AN XY:

132696

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1456188

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

724558

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000209

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151338

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73828

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000197

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000670

Hom.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Oct 07, 2024

The c.592C>T (p.R198C) alteration is located in exon 4 (coding exon 4) of the FOSL2 gene. This alteration results from a C to T substitution at nucleotide position 592, causing the arginine (R) at amino acid position 198 to be replaced by a cysteine (C). 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

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

.;T;T

Eigen

Benign

-0.033

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.2

.;L;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.41

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.063

T;T;T

Sift4G

Uncertain

0.057

T;T;T

Polyphen

0.0070

.;B;.

Vest4

0.43

MVP

0.92

MPC

0.35

ClinPred

0.088

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.69

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