2-28412127-GGT-G

Position:

• chr2-28412127-GGT-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_005253.4(FOSL2):​c.662_663delTG​(p.Val221fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOSL2 NM_005253.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.67

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.325 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-28412127-GGT-G is Pathogenic according to our data. Variant chr2-28412127-GGT-G is described in ClinVar as [Pathogenic]. Clinvar id is 3242359.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOSL2	NM_005253.4	c.662_663delTG	p.Val221fs	frameshift_variant	4/4	ENST00000264716.9	NP_005244.1
FOSL2	XM_006711976.4	c.713_714delTG	p.Val238fs	frameshift_variant	4/4		XP_006712039.1
FOSL2	XM_006711977.4	c.596_597delTG	p.Val199fs	frameshift_variant	4/4		XP_006712040.1
FOSL2	XM_005264231.5	c.*147_*148delTG		3_prime_UTR_variant	5/5		XP_005264288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOSL2	ENST00000264716.9	c.662_663delTG	p.Val221fs	frameshift_variant	4/4	1	NM_005253.4	ENSP00000264716.4
FOSL2	ENST00000379619.5	c.638_639delTG	p.Val213fs	frameshift_variant	4/4	1		ENSP00000368939.1
FOSL2	ENST00000436647.1	c.545_546delTG	p.Val182fs	frameshift_variant	4/4	2		ENSP00000396497.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Aplasia cutis-enamel dysplasia syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 18, 2024

- -

Computational scores

Source: dbNSFP v4.3

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: chr2-28634994;