SPRED2

sprouty related EVH1 domain containing 2

Basic information

Region (hg38): 2:65310850-65432637

Links

ENSG00000198369 ∙ NCBI:200734 ∙ OMIM:609292 ∙ HGNC:17722 ∙ Uniprot:Q7Z698 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Noonan syndrome 14 (Limited), mode of inheritance: AR
• Noonan syndrome 14 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Noonan syndrome 14	AR	Cardiovascular; Hematologic; Oncologic	Surveillance and treatment related to manifestations such as cardiac anomalies (which include cardiomyopathy and structural anomalies) may be beneficial; The disorder can include bleeding diathesis, and recognition and preventive measures (eg, in surgical situations) may be beneficial	Cardiovascular; Craniofacial; Genitourinary; Hematologic; Musculoskeletal; Neurologic	34626534

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPRED2 gene.

• Inborn genetic diseases (18 variants)
• not provided (3 variants)
• Noonan syndrome 14 (2 variants)
• Noonan syndrome (2 variants)
• Severe postnatal growth retardation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPRED2 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					1	1
missense	1		18			19
nonsense						0
start loss						0
frameshift	1		1			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				1		1
Total	2	0	19	1	1

Variants in SPRED2

This is a list of pathogenic ClinVar variants found in the SPRED2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-65313538-C-T		not specified	Uncertain significance (Jul 15, 2021)
2-65313565-C-T		not specified	Uncertain significance (Oct 13, 2023)
2-65313614-TAA-T		Noonan syndrome • Noonan syndrome 14	Pathogenic (Aug 01, 2021)
2-65313620-C-T		not specified	Uncertain significance (Aug 17, 2022)
2-65313653-T-C		not specified	Uncertain significance (Jun 06, 2023)
2-65313669-G-T		not specified	Uncertain significance (Mar 01, 2024)
2-65313726-C-G		not specified	Uncertain significance (Jun 22, 2023)
2-65313808-T-A		not specified	Uncertain significance (Dec 18, 2023)
2-65313815-T-A		not specified	Uncertain significance (Sep 21, 2023)
2-65313815-T-G		not specified	Uncertain significance (Dec 18, 2023)
2-65313827-A-G		not specified	Uncertain significance (Sep 25, 2023)
2-65313841-C-T		not specified	Uncertain significance (Jan 09, 2024)
2-65313866-G-A		not specified	Uncertain significance (Apr 25, 2023)
2-65313910-C-T		not specified	Uncertain significance (Sep 17, 2021)
2-65313990-C-G		not specified	Uncertain significance (Jan 23, 2023)
2-65314030-G-A		not specified	Uncertain significance (Jan 04, 2024)
2-65314162-G-C		not specified	Uncertain significance (May 25, 2022)
2-65314163-G-A		not specified	Uncertain significance (Feb 02, 2022)
2-65314177-G-A			Likely benign (Oct 01, 2023)
2-65316739-C-G		not specified	Uncertain significance (May 03, 2023)
2-65316749-G-T		not specified	Uncertain significance (Mar 12, 2024)
2-65316754-C-T		not specified	Uncertain significance (Apr 25, 2022)
2-65316798-C-T		not specified	Uncertain significance (Aug 21, 2023)
2-65316832-G-A		not specified	Uncertain significance (Mar 07, 2024)
2-65316858-G-A		not specified	Uncertain significance (Aug 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPRED2	protein_coding	protein_coding	ENST00000356388	6	121787

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.87e-7	0.765	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.31	234	297	0.787	0.0000210	2752
Missense in Polyphen		64	113.38	0.56448		1045
Synonymous	0.966	116	130	0.892	0.0000106	798
Loss of Function	1.33	13	19.3	0.673	0.00000110	203

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000789	0.000786
Ashkenazi Jewish	0.00	0.00
East Asian	0.000218	0.000217
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000251	0.000246
Middle Eastern	0.000218	0.000217
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negatively regulates Ras signaling pathways and downstream activation of MAP kinases. {ECO:0000269|PubMed:15683364}.
• Pathway: Imatinib and Chronic Myeloid Leukemia;Signal Transduction;Signaling by FGFR;Regulation of RAS by GAPs;KitReceptor;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Signaling by Receptor Tyrosine Kinases;Signaling events mediated by Stem cell factor receptor (c-Kit);FGFRL1 modulation of FGFR1 signaling;Signaling by FGFR1 (Consensus)

Recessive Scores

• pRec: 0.130

Intolerance Scores

• loftool: 0.377
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.2

Haploinsufficiency Scores

• pHI: 0.513
• hipred: Y
• hipred_score: 0.543
• ghis: 0.599

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.886

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spred2
• Phenotype: limbs/digits/tail phenotype; skeleton phenotype; reproductive system phenotype; hematopoietic system phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: inactivation of MAPK activity;multicellular organism development;fibroblast growth factor receptor signaling pathway;negative regulation of peptidyl-threonine phosphorylation;positive regulation of DNA damage response, signal transduction by p53 class mediator;regulation of protein deacetylation
• Cellular component: cytosol;plasma membrane;transport vesicle membrane
• Molecular function: stem cell factor receptor binding;protein binding;protein kinase binding;protein serine/threonine kinase inhibitor activity