rs12624279

Variant names:

• chr2-28411923-G-A
• rs12624279
• ENST00000379619.5:c.432G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-28411923-G-A
• chr2-28411923-G-C
• chr2-28411923-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000379619.5(FOSL2):​c.432G>A​(p.Pro144Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,613,402 control chromosomes in the GnomAD database, including 134,510 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 0.34 (9639 hom., cov: 32)
  • Exomes 𝑓: 0.41 (124871 hom.)
• Consequence: FOSL2 ENST00000379619.5 synonymous
• Scores: Splicing: ADA: 0.00002265
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 21 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-1.23 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOSL2	NM_005253.4	c.463-7G>A		splice_region_variant, intron_variant	Intron 3 of 3	ENST00000264716.9	NP_005244.1
FOSL2	XM_006711976.4	c.507G>A	p.Pro169Pro	synonymous_variant	Exon 4 of 4		XP_006712039.1
FOSL2	XM_006711977.4	c.390G>A	p.Pro130Pro	synonymous_variant	Exon 4 of 4		XP_006712040.1
FOSL2	XM_005264231.5	c.566-7G>A		splice_region_variant, intron_variant	Intron 4 of 4		XP_005264288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOSL2	ENST00000379619.5	c.432G>A	p.Pro144Pro	synonymous_variant	Exon 4 of 4	1		ENSP00000368939.1
FOSL2	ENST00000264716.9	c.463-7G>A		splice_region_variant, intron_variant	Intron 3 of 3	1	NM_005253.4	ENSP00000264716.4
FOSL2	ENST00000436647.1	c.346-7G>A		splice_region_variant, intron_variant	Intron 3 of 3	2		ENSP00000396497.1

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52385 AN: 152014 Hom.: 9646 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.317

GnomAD2 exomes AF: 0.360 AC: 89691 AN: 249356 AF XY: 0.373

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.283

Gnomad EAS exome AF: 0.189

Gnomad FIN exome AF: 0.411

Gnomad NFE exome AF: 0.404

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.408 AC: 596040 AN: 1461270 Hom.: 124871 Cov.: 41 AF XY: 0.410 AC XY: 297840 AN XY: 726958

African (AFR) AF: 0.234 AC: 7818 AN: 33472

American (AMR) AF: 0.258 AC: 11548 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 7586 AN: 26128

East Asian (EAS) AF: 0.188 AC: 7482 AN: 39696

South Asian (SAS) AF: 0.467 AC: 40255 AN: 86228

European-Finnish (FIN) AF: 0.423 AC: 22577 AN: 53386

Middle Eastern (MID) AF: 0.257 AC: 1476 AN: 5754

European-Non Finnish (NFE) AF: 0.426 AC: 474042 AN: 1111520

Other (OTH) AF: 0.385 AC: 23256 AN: 60368

GnomAD4 genome AF: 0.344 AC: 52386 AN: 152132 Hom.: 9639 Cov.: 32 AF XY: 0.343 AC XY: 25508 AN XY: 74376

African (AFR) AF: 0.245 AC: 10186 AN: 41504

American (AMR) AF: 0.277 AC: 4230 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1028 AN: 3468

East Asian (EAS) AF: 0.195 AC: 1011 AN: 5174

South Asian (SAS) AF: 0.451 AC: 2178 AN: 4828

European-Finnish (FIN) AF: 0.413 AC: 4367 AN: 10580

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28202 AN: 67962

Other (OTH) AF: 0.318 AC: 673 AN: 2116

Alfa AF: 0.382 Hom.: 52409

Bravo AF: 0.328

Asia WGS AF: 0.304 AC: 1057 AN: 3478

EpiCase AF: 0.389

EpiControl AF: 0.394

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.51
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0020
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: rs12624279; hg19: chr2-28634790; COSMIC: COSV53104684; COSMIC: COSV53104684;