Variant chr2-28412105-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005253.4(FOSL2):c.638G>C(p.Gly213Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000934 in 1,606,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

FOSL2
NM_005253.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.165

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019889712).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOSL2	NM_005253.4 linkuse as main transcript	c.638G>C	p.Gly213Ala	missense_variant	4/4	ENST00000264716.9	NP_005244.1	P15408-1Q9H5M2
FOSL2	XM_006711976.4 linkuse as main transcript	c.689G>C	p.Gly230Ala	missense_variant	4/4		XP_006712039.1
FOSL2	XM_006711977.4 linkuse as main transcript	c.572G>C	p.Gly191Ala	missense_variant	4/4		XP_006712040.1
FOSL2	XM_005264231.5 linkuse as main transcript	c.*123G>C		3_prime_UTR_variant	5/5		XP_005264288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FOSL2	ENST00000264716.9 linkuse as main transcript	c.638G>C	p.Gly213Ala	missense_variant	4/4	1	NM_005253.4	ENSP00000264716.4	P15408-1
FOSL2	ENST00000379619.5 linkuse as main transcript	c.614G>C	p.Gly205Ala	missense_variant	4/4	1		ENSP00000368939.1	P15408-2
FOSL2	ENST00000436647.1 linkuse as main transcript	c.521G>C	p.Gly174Ala	missense_variant	4/4	2		ENSP00000396497.1	C9JCN8

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152152

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:

0.000580

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000538

AC:

AN:

241532

Hom.:

AF XY:

0.0000608

AC XY:

AN XY:

131622

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000712

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000825

AC:

AN:

1454076

Hom.:

Cov.:

AF XY:

0.00000968

AC XY:

AN XY:

723496

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000581

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000495

AC:

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

Aug 06, 2024

The c.638G>C (p.G213A) alteration is located in exon 4 (coding exon 4) of the FOSL2 gene. This alteration results from a G to C substitution at nucleotide position 638, causing the glycine (G) at amino acid position 213 to be replaced by an alanine (A). 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

0.066

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.38

CADD

Benign

3.4

DANN

Benign

0.21

DEOGEN2

Benign

0.17

.;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.59

T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

.;N;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.56

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.78

T;T;T

Sift4G

Benign

0.81

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.090

MutPred

0.19

.;Loss of sheet (P = 0.1158);.;

MVP

0.61

MPC

0.28

ClinPred

0.0080

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.35

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