NM_005253.4:c.628C>G

Variant names:

• chr2-28412095-C-G
• rs767175362
• NM_005253.4:c.628C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005253.4(FOSL2):​c.628C>G​(p.Arg210Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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)
• Consequence: FOSL2 NM_005253.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.99

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38460436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOSL2	NM_005253.4	c.628C>G	p.Arg210Gly	missense_variant	Exon 4 of 4	ENST00000264716.9	NP_005244.1
FOSL2	XM_006711976.4	c.679C>G	p.Arg227Gly	missense_variant	Exon 4 of 4		XP_006712039.1
FOSL2	XM_006711977.4	c.562C>G	p.Arg188Gly	missense_variant	Exon 4 of 4		XP_006712040.1
FOSL2	XM_005264231.5	c.*113C>G		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.628C>G	p.Arg210Gly	missense_variant	Exon 4 of 4	1	NM_005253.4	ENSP00000264716.4
FOSL2	ENST00000379619.5	c.604C>G	p.Arg202Gly	missense_variant	Exon 4 of 4	1		ENSP00000368939.1
FOSL2	ENST00000436647.1	c.511C>G	p.Arg171Gly	missense_variant	Exon 4 of 4	2		ENSP00000396497.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000413 AC: 1 AN: 242182 Hom.: 0 AF XY: 0.00000758 AC XY: 1 AN XY: 131930

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000910

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	.;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.9	.;L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.55	N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.29	T;T;D
Sift4G	Benign	0.30	T;T;T
Polyphen		1.0	.;D;.
Vest4		0.24
MutPred		0.28		.;Loss of methylation at R210 (P = 0.0427);.;
MVP		0.64
MPC		0.90
ClinPred		0.53	D
GERP RS		4.3
Varity_R		0.12
gMVP		0.76

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

Other links and lift over

dbSNP: rs767175362; hg19: chr2-28634962;