chr3-138945767-GGCGGCGGC-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_023067.4(FOXL2):​c.948_955del​(p.Pro317GlyfsTer214) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

FOXL2
NM_023067.4 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 1.44
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 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 7 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 3-138945767-GGCGGCGGC-G is Pathogenic according to our data. Variant chr3-138945767-GGCGGCGGC-G is described in ClinVar as [Pathogenic]. Clinvar id is 634987.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FOXL2NM_023067.4 linkuse as main transcriptc.948_955del p.Pro317GlyfsTer214 frameshift_variant 1/1 ENST00000648323.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FOXL2ENST00000648323.1 linkuse as main transcriptc.948_955del p.Pro317GlyfsTer214 frameshift_variant 1/1 NM_023067.4 P1

Frequencies

GnomAD3 genomes
Cov.:
33
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Blepharophimosis, ptosis, and epicanthus inversus syndrome Pathogenic:2
Pathogenic, no assertion criteria providedclinical testingWessex Regional Genetics Laboratory, Salisbury District HospitalJan 01, 2011- -
Pathogenic, criteria provided, single submitterclinical testingMendelicsMay 28, 2019- -

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.

Other links and lift over

dbSNP: rs1576469579; hg19: chr3-138664609; API