chr2-28412075-C-A

Variant names:

• chr2-28412075-C-A
• NM_005253.4:c.608C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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]

ACMG classification

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
FOSL2	NM_005253.4	c.608C>A	p.Ala203Asp	missense_variant	Exon 4 of 4	ENST00000264716.9	NP_005244.1
FOSL2	XM_006711976.4	c.659C>A	p.Ala220Asp	missense_variant	Exon 4 of 4		XP_006712039.1
FOSL2	XM_006711977.4	c.542C>A	p.Ala181Asp	missense_variant	Exon 4 of 4		XP_006712040.1
FOSL2	XM_005264231.5	c.*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
FOSL2	ENST00000264716.9	c.608C>A	p.Ala203Asp	missense_variant	Exon 4 of 4	1	NM_005253.4	ENSP00000264716.4
FOSL2	ENST00000379619.5	c.584C>A	p.Ala195Asp	missense_variant	Exon 4 of 4	1		ENSP00000368939.1
FOSL2	ENST00000436647.1	c.491C>A	p.Ala164Asp	missense_variant	Exon 4 of 4	2		ENSP00000396497.1

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

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;