rs797044532

chr3-138945851-TGGGGGTGCGGCGGAGGC-Tchr3-138945851-TGGGGGTGCGGCGGAGGC-TGGGGGTGCGGCGGAGGCGGGGGTGCGGCGGAGGC

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Strong PP5

The NM_023067.4(FOXL2):c.855_871del(p.Pro287AlafsTer241) variant causes a frameshift change. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXL2 NM_023067.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2 O:1
• Conservation: PhyloP100: 6.77

Genes affected

FOXL2 (HGNC:1092): (forkhead box L2) This gene encodes a forkhead transcription factor. The protein contains a fork-head DNA-binding domain and may play a role in ovarian development and function. Expansion of a polyalanine repeat region and other mutations in this gene are a cause of blepharophimosis syndrome and premature ovarian failure 3. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 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. There are 18 pathogenic variants in the truncated region.
• PP5: Variant 3-138945851-TGGGGGTGCGGCGGAGGC-T is Pathogenic according to our data. Variant chr3-138945851-TGGGGGTGCGGCGGAGGC-T is described in ClinVar as [Pathogenic]. Clinvar id is 4859.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXL2	NM_023067.4	c.855_871del	p.Pro287AlafsTer241	frameshift_variant	1/1	ENST00000648323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXL2	ENST00000648323.1	c.855_871del	p.Pro287AlafsTer241	frameshift_variant	1/1		NM_023067.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.24e-7 AC: 1 AN: 1082272 Hom.: 0 AF XY: 0.00000195 AC XY: 1 AN XY: 512570

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Blepharophimosis, ptosis, and epicanthus inversus syndrome Pathogenic:1 Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Pathogenic, no assertion criteria provided	clinical testing	Wessex Regional Genetics Laboratory, Salisbury District Hospital	Jan 01, 2018	- -

BLEPHAROPHIMOSIS, PTOSIS, AND EPICANTHUS INVERSUS, TYPE II Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs797044532; hg19: chr3-138664693;