AAR2

protein-coding

AAR2 splicing factor

Gene summary

This gene encodes the homolog of the yeast A1-alpha2 repressin protein that is involved in mRNA splicing. Alternately spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

Previous symbols:

C20orf4

MANE transcript

NM_001271874.2

Inheritance

ClinVar variants

P:1U:57B:4

Top phenotype

Hypoplasia of the corpus callosum

gnomAD constraint

pLI —, LoF o/e 0.77

Max pathogenic AF

—

Genomic locus

chr20:36,236,131-36,270,918

External References & Databases

Ensembl (ENSG00000131043)

Transcript & Mutation Effects

hg38 • Region Span ~34.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

multiple congenital anomalies/dysmorphic syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019042

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AAR2 variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 2

Hypoplasia of the corpus callosumTotal: 1

MaculeTotal: 1

Ventricular septal defectTotal: 1

Cerebellar malformationTotal: 1

Global developmental delayTotal: 1

MicrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001271874.2. 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				1 clinvar		1
missense		1 clinvar	56 clinvar	3 clinvar		60
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	57	4	0	62

Highest pathogenic variant AF is 0.000026018371

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 59 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001271874.2	RefSeq	NP_001258803.1	3	MANE Select
ENST00000320849.9	Ensembl	ENSP00000313674.4	3	MANE Select
NM_015511.5	RefSeq	NP_056326.2	3	Standard
ENST00000373932.3	Ensembl	ENSP00000363043.3	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

spliceosomal tri-snRNP complex assembly

Cellular Component

spliceosomal complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373932
Coding exons: 3
Length: 34460
Individuals with no LoFs: 125553
Homozygous LoFs: 0
Heterozygous LoFs: 195
Defined: 125748
p: 0.000776

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.855	190	226	0.840	0.0000135	2535
Missense (PolyPhen)		66	86.022	0.76724		995
Synonymous	0.790	83	92.7	0.896	0.00000552	772
Loss of Function	0.715	9	11.6	0.774	5.70e-7	135

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00040	0.00040	rare
Ashkenazi Jewish	0.0013	0.0013	notable
East Asian	0	0.0	absent
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.0013	0.0013	notable
South Asian	0.00029	0.00029	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the U5 snRNP complex that is required for spliceosome assembly and for pre-mRNA splicing. {ECO:0000250|UniProtKB:P32357}.;

Recessive Scores

pRec: 0.0869

Intolerance Scores

RVIS EVS: -0.31
RVIS percentile EVS: 32.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N

Gene Damage Prediction

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