rs1553752849

Positions:

• chr3-138946022-G-GGCGGCTGCAGCCGCAGCTGCTGCAGCCGCT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PP5_Moderate BP3

The NM_023067.4(FOXL2):​c.700_701insAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC​(p.Ala234delinsGluArgLeuGlnGlnLeuArgLeuGlnProPro) variant causes a protein altering 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: 32)
• Consequence: FOXL2 NM_023067.4 protein_altering
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.32

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-138946022-G-GGCGGCTGCAGCCGCAGCTGCTGCAGCCGCT is Pathogenic according to our data. Variant chr3-138946022-G-GGCGGCTGCAGCCGCAGCTGCTGCAGCCGCT is described in ClinVar as [Pathogenic]. Clinvar id is 559900.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP3: Nonframeshift variant in repetitive region in NM_023067.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXL2	NM_023067.4	c.700_701insAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC	p.Ala234delinsGluArgLeuGlnGlnLeuArgLeuGlnProPro	protein_altering_variant	1/1	ENST00000648323.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXL2	ENST00000648323.1	c.700_701insAGCGGCTGCAGCAGCTGCGGCTGCAGCCGC	p.Ala234delinsGluArgLeuGlnGlnLeuArgLeuGlnProPro	protein_altering_variant	1/1		NM_023067.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Blepharophimosis, ptosis, and epicanthus inversus syndrome Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Equipe Genetique des Anomalies du Developpement, Université de Bourgogne

Jul 29, 2014

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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: rs1553752849; hg19: chr3-138664864;