rs1285238959

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005253.4(FOSL2):​c.608C>A​(p.Ala203Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A203T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FOSL2
NM_005253.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.74
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.053512067).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOSL2NM_005253.4 linkc.608C>A p.Ala203Asp missense_variant Exon 4 of 4 ENST00000264716.9 NP_005244.1 P15408-1Q9H5M2
FOSL2XM_006711976.4 linkc.659C>A p.Ala220Asp missense_variant Exon 4 of 4 XP_006712039.1
FOSL2XM_006711977.4 linkc.542C>A p.Ala181Asp missense_variant Exon 4 of 4 XP_006712040.1
FOSL2XM_005264231.5 linkc.*93C>A 3_prime_UTR_variant Exon 5 of 5 XP_005264288.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOSL2ENST00000264716.9 linkc.608C>A p.Ala203Asp missense_variant Exon 4 of 4 1 NM_005253.4 ENSP00000264716.4 P15408-1
FOSL2ENST00000379619.5 linkc.584C>A p.Ala195Asp missense_variant Exon 4 of 4 1 ENSP00000368939.1 P15408-2
FOSL2ENST00000436647.1 linkc.491C>A p.Ala164Asp missense_variant Exon 4 of 4 2 ENSP00000396497.1 C9JCN8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455060
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
724040
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.091
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
14
DANN
Benign
0.94
DEOGEN2
Benign
0.20
.;T;T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.71
T;T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.054
T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.34
.;N;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.78
N;N;N
REVEL
Benign
0.17
Sift
Benign
0.18
T;T;T
Sift4G
Benign
0.34
T;T;T
Polyphen
0.0
.;B;.
Vest4
0.19
MutPred
0.11
.;Loss of catalytic residue at A203 (P = 0.1989);.;
MVP
0.28
MPC
0.41
ClinPred
0.068
T
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.21
gMVP
0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-28634942; API