chr2-28395294-G-A

Variant names:

• chr2-28395294-G-A
• rs12473028
• NM_005253.4:c.102+1472G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005253.4(FOSL2):​c.102+1472G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,124 control chromosomes in the GnomAD database, including 11,795 homozygotes. 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: 𝑓 0.39 (11795 hom., cov: 32)
• Consequence: FOSL2 NM_005253.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

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.102+1472G>A		intron	N/A	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.102+1472G>A		intron	N/A	ENSP00000264716.4	P15408-1
	FOSL2	ENST00000379619.5	TSL:1	c.27+2458G>A		intron	N/A	ENSP00000368939.1	P15408-2
	FOSL2	ENST00000902793.1		c.102+1472G>A		intron	N/A	ENSP00000572852.1

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59335 AN: 152006 Hom.: 11783 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.365

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.390 AC: 59388 AN: 152124 Hom.: 11795 Cov.: 32 AF XY: 0.388 AC XY: 28876 AN XY: 74378

African (AFR) AF: 0.402 AC: 16678 AN: 41484

American (AMR) AF: 0.304 AC: 4642 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3472

East Asian (EAS) AF: 0.219 AC: 1133 AN: 5174

South Asian (SAS) AF: 0.473 AC: 2281 AN: 4822

European-Finnish (FIN) AF: 0.395 AC: 4180 AN: 10588

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28294 AN: 67978

Other (OTH) AF: 0.364 AC: 769 AN: 2112

Alfa AF: 0.395 Hom.: 15401

Bravo AF: 0.382

Asia WGS AF: 0.339 AC: 1181 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.71
PhyloP100		0.080
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs12473028; hg19: chr2-28618161;