Genetic Variant FOXL2:p.Ala229_Ala233dup (chr3-138946024-G-GGCTGCAGCCGCAGCT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP3

The NM_023067.4(FOXL2):c.684_698dupAGCTGCGGCTGCAGC(p.Ala229_Ala233dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00000242 in 1,237,130 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

FOXL2
NM_023067.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.30

Variant links:

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]

FOXL2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 3-138946024-G-GGCTGCAGCCGCAGCT is Pathogenic according to our data. Variant chr3-138946024-G-GGCTGCAGCCGCAGCT is described in ClinVar as [Pathogenic]. Clinvar id is 4870.Status of the report is no_assertion_criteria_provided, 0 stars.

BP3

Nonframeshift variant in repetitive region in NM_023067.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXL2	NM_023067.4 link	c.684_698dupAGCTGCGGCTGCAGC	p.Ala229_Ala233dup	disruptive_inframe_insertion	Exon 1 of 1	ENST00000648323.1	NP_075555.1	P58012Q53ZD3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXL2	ENST00000648323.1 link	c.684_698dupAGCTGCGGCTGCAGC	p.Ala229_Ala233dup	disruptive_inframe_insertion	Exon 1 of 1		NM_023067.4	ENSP00000497217.1		P58012

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000242

AC:

AN:

1237130

Hom.:

Cov.:

AF XY:

0.00000330

AC XY:

AN XY:

606128

show subpopulations

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:

0.00000197

Gnomad4 OTH exome

AF:

0.0000197

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BLEPHAROPHIMOSIS, PTOSIS, AND EPICANTHUS INVERSUS, TYPE I

Pathogenic:1

Mar 01, 2007

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

3-138946024-GGCTGCAGCCGCAGCT-GGCTGCAGCCGCAGCTGCTGCAGCCGCAGCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over