2-28393736-C-G

Variant names:

• chr2-28393736-C-G
• NM_005253.4:c.16C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005253.4(FOSL2):​c.16C>G​(p.Pro6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,808 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.

• 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: 2.67

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-AS1 (HGNC:55784): (FOSL2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09488267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOSL2	NM_005253.4	c.16C>G	p.Pro6Ala	missense_variant	Exon 1 of 4	ENST00000264716.9	NP_005244.1
FOSL2	XM_006711976.4	c.16C>G	p.Pro6Ala	missense_variant	Exon 1 of 4		XP_006712039.1
FOSL2	XM_005264231.5	c.16C>G	p.Pro6Ala	missense_variant	Exon 1 of 5		XP_005264288.1
FOSL2-AS1	NR_103831.1	n.125+812G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOSL2	ENST00000264716.9	c.16C>G	p.Pro6Ala	missense_variant	Exon 1 of 4	1	NM_005253.4	ENSP00000264716.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457808 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725166

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.040
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.070
Sift	Benign	0.41	T
Sift4G	Benign	0.27	T
Polyphen		0.0050	B
Vest4		0.15
MutPred		0.20		Loss of stability (P = 0.0898);
MVP		0.28
MPC		0.74
ClinPred		0.61	D
GERP RS		4.8
Varity_R		0.15
gMVP		0.60

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: chr2-28616603;