2-28412095-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R210C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOSL2 NM_005253.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.99
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• aplasia cutis-enamel dysplasia syndrome

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005253.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOSL2	NM_005253.4	MANE Select	c.628C>G	p.Arg210Gly	missense	Exon 4 of 4	NP_005244.1	P15408-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOSL2	ENST00000264716.9	TSL:1 MANE Select	c.628C>G	p.Arg210Gly	missense	Exon 4 of 4	ENSP00000264716.4	P15408-1
	FOSL2	ENST00000379619.5	TSL:1	c.604C>G	p.Arg202Gly	missense	Exon 4 of 4	ENSP00000368939.1	P15408-2
	FOSL2	ENST00000902793.1		c.679C>G	p.Arg227Gly	missense	Exon 4 of 4	ENSP00000572852.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000413 AC: 1 AN: 242182 AF XY: 0.00000758

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 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 v4.9

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
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.0
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.55	N
REVEL	Uncertain	0.33
Sift	Benign	0.29	T
Sift4G	Benign	0.30	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
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

dbSNP: rs767175362; hg19: chr2-28634962;