Variant rs28937885 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_023067.4(FOXL2):c.772T>A(p.Tyr258Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000709 in 1,409,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

FOXL2
NM_023067.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 1.83

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.867

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXL2	NM_023067.4 linkuse as main transcript	c.772T>A	p.Tyr258Asn	missense_variant	1/1	ENST00000648323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXL2	ENST00000648323.1 linkuse as main transcript	c.772T>A	p.Tyr258Asn	missense_variant	1/1		NM_023067.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000715

AC:

AN:

1259114

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

617976

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:

0.00000682

Gnomad4 OTH exome

AF:

0.0000388

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73678

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000919

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Premature ovarian failure 3

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2002

- -

Blepharophimosis, ptosis, and epicanthus inversus syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

Cadd

Uncertain

Dann

Benign

0.96

DEOGEN2

Benign

0.36

T;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.065

FATHMM_MKL

Uncertain

0.77

M_CAP

Pathogenic

0.80

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Uncertain

0.74

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.93

Polyphen

1.0

D;D

Vest4

0.75

MutPred

0.77

Loss of phosphorylation at Y258 (P = 0.0085);Loss of phosphorylation at Y258 (P = 0.0085);

MVP

0.93

ClinPred

0.27

GERP RS

2.2

Varity_R

0.38

gMVP

0.70

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

LitVar

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

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