LEFTY2

left-right determination factor 2, the group of Transforming growth factor beta superfamily

Basic information

Region (hg38): 1:225936597-225941383

Previous symbols: [ "TGFB4", "EBAF" ]

Links

ENSG00000143768 ∙ NCBI:7044 ∙ OMIM:601877 ∙ HGNC:3122 ∙ Uniprot:O00292 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital heart disease (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Left-right axis malformations	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Pulmonary	10053005
The contributions of variants to clinical disease are unclear

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LEFTY2 gene.

• Left-right axis malformations (107 variants)
• not provided (16 variants)
• not specified (11 variants)
• Inborn genetic diseases (11 variants)
• LEFTY2-related condition (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LEFTY2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	34	9	45
missense			45	4	3	52
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			9	6	10	25
Total	0	0	57	44	22

Variants in LEFTY2

This is a list of pathogenic ClinVar variants found in the LEFTY2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-225936711-A-G		Left-right axis malformations	Uncertain significance (Jan 13, 2018)
1-225936870-G-A		Left-right axis malformations	Benign (Jan 13, 2018)
1-225936870-G-C		Left-right axis malformations	Uncertain significance (Jan 13, 2018)
1-225936945-A-C		Left-right axis malformations	Likely benign (Apr 27, 2017)
1-225937124-G-C		Left-right axis malformations	Likely benign (Apr 27, 2017)
1-225937144-T-A		Left-right axis malformations	Uncertain significance (Jan 12, 2018)
1-225937162-C-T		Left-right axis malformations	Uncertain significance (Jan 13, 2018)
1-225937181-G-A		Left-right axis malformations	Uncertain significance (Jan 12, 2018)
1-225937212-G-A		Left-right axis malformations	Likely benign (Apr 28, 2017)
1-225937291-A-C		Left-right axis malformations	Uncertain significance (Jan 13, 2018)
1-225937377-A-T		Left-right axis malformations	Uncertain significance (Jan 12, 2018)
1-225937405-C-T		Left-right axis malformations	Uncertain significance (Jan 13, 2018)
1-225937465-G-A		Left-right axis malformations	Benign/Likely benign (Aug 04, 2023)
1-225937467-G-A		not specified	Uncertain significance (Mar 01, 2024)
1-225937468-C-A		Left-right axis malformations	Likely benign (Jan 16, 2020)
1-225937469-G-A		Left-right axis malformations • not specified	Conflicting classifications of pathogenicity (Mar 02, 2023)
1-225937471-C-T		Left-right axis malformations	Benign (Aug 15, 2021)
1-225937476-C-T		Left-right axis malformations • not specified	Uncertain significance (Jul 10, 2023)
1-225937478-G-A		not specified	Uncertain significance (Dec 27, 2023)
1-225937495-C-A		Left-right axis malformations	Uncertain significance (Jan 19, 2024)
1-225937501-C-A		Left-right axis malformations	Uncertain significance (Oct 05, 2023)
1-225937506-T-G		Left-right axis malformations	Uncertain significance (Aug 05, 2022)
1-225937507-G-A		Left-right axis malformations • not specified • LEFTY2-related disorder	Benign (Dec 15, 2023)
1-225937512-G-T		not specified	Conflicting classifications of pathogenicity (May 04, 2022)
1-225937517-C-T		Left-right axis malformations	Uncertain significance (Oct 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LEFTY2	protein_coding	protein_coding	ENST00000366820	4	4892

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000293	0.945	125699	0	18	125717	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.579	214	239	0.895	0.0000157	2302
Missense in Polyphen		43	65.797	0.65353		702
Synonymous	-0.210	125	122	1.02	0.00000918	793
Loss of Function	1.72	8	15.2	0.525	8.29e-7	132

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000120	0.000114
Middle Eastern	0.00	0.00
South Asian	0.000110	0.0000980
Other	0.000174	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for left-right (L-R) asymmetry determination of organ systems in mammals. May play a role in endometrial bleeding.
• Disease: DISEASE: Left-right axis malformations (LRAM) [MIM:601877]: The defect includes left pulmonary isomerism, with cardiac anomalies characterized by complete atrioventricular canal defect and hypoplastic left ventricle, and interrupted inferior vena cava. {ECO:0000269|PubMed:10053005}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: TGF-beta signaling pathway - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Cell Differentiation - Index expanded;Cell Differentiation - Index;Mesodermal Commitment Pathway;BMP2-WNT4-FOXO1 Pathway in Human Primary Endometrial Stromal Cell Differentiation;TGF-beta Receptor Signaling;Developmental Biology;Regulation of signaling by NODAL;Signaling by NODAL;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.527

Intolerance Scores

• loftool: 0.266
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.27

Haploinsufficiency Scores

• pHI: 0.578
• hipred: N
• hipred_score: 0.305

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Lefty2
• Phenotype: immune system phenotype; digestive/alimentary phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; embryo phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: lft2
• Affected structure: endodermal cell
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: platelet degranulation;transforming growth factor beta receptor signaling pathway;multicellular organism development;regulation of signaling receptor activity;positive regulation of pathway-restricted SMAD protein phosphorylation;regulation of apoptotic process;regulation of MAPK cascade;cell development;SMAD protein signal transduction
• Cellular component: extracellular region;extracellular space;platelet alpha granule lumen;collagen-containing extracellular matrix
• Molecular function: cytokine activity;transforming growth factor beta receptor binding;growth factor activity