SALL2

protein-coding

spalt like transcription factor 2, the group of Zinc fingers C2H2-type

Gene summary

This gene encodes a protein containing multiple zinc finger domains. The encoded protein functions in optical fissure closure during development of the eye in the embryo. Mutations in this gene are associated with ocular coloboma. [provided by RefSeq, Jul 2016]

MANE transcript

NM_001364564.1

Inheritance

ClinVar variants

P:1U:151B:47

Top phenotype

Coloboma, ocular, autosomal recessive

gnomAD constraint

pLI —, LoF o/e 0.42

Max pathogenic AF

—

Genomic locus

chr14:21,521,080-21,537,216

External References & Databases

Ensembl (ENSG00000165821)

Transcript & Mutation Effects

hg38 • Region Span ~16.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

coloboma, ocular, autosomal recessiveLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0009002

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Coloboma, ocular, autosomal recessiveAR

Manifestation: Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 24412933

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SALL2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 137

not providedTotal: 73

SALL2-related disorderTotal: 17

Coloboma, ocular, autosomal recessiveTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001364564.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				27 clinvar	4 clinvar	31
missense			151 clinvar	9 clinvar	7 clinvar	167
nonsense	1 clinvar					1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	0	151	36	11	199

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001364564.1	RefSeq	NP_001351493.1	2	MANE Select
ENST00000537235.2	Ensembl	ENSP00000438493.2	2	MANE Select
NM_001291446.2	RefSeq	NP_001278375.1	4	Standard
NM_001291447.2	RefSeq	NP_001278376.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
eye development
regulation of transcription, DNA-templated
neural tube development
positive regulation of transcription by RNA polymerase II

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
protein binding
protein-containing complex binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000327430
Coding exons: 2
Length: 16119
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125748
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.715	527	575	0.916	0.0000313	6439
Missense (PolyPhen)		224	294.84	0.75974		3350
Synonymous	-0.842	255	238	1.07	0.0000134	2228
Loss of Function	2.76	11	26.3	0.418	0.00000138	321

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0.00052	0.00050	rare
East Asian	0.00027	0.00016	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable transcription factor that plays a role in eye development before, during, and after optic fissure closure. {ECO:0000269|PubMed:24412933}.;
Disease: DISEASE: Coloboma, ocular, autosomal recessive (COAR) [MIM:216820]: An ocular anomaly resulting from abnormal morphogenesis of the optic cup and stalk, and incomplete fusion of the fetal intra-ocular fissure during gestation. The clinical presentation is variable. Some individuals may present with minimal defects in the anterior iris leaf without other ocular defects. More complex malformations create a combination of iris, uveoretinal and/or optic nerve defects without or with microphthalmia or even anophthalmia. {ECO:0000269|PubMed:24412933}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.659
RVIS EVS: 0.5
RVIS percentile EVS: 79.64

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.607

Gene Damage Prediction

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