SRRM2

serine/arginine repetitive matrix 2, the group of Spliceosomal C complex|Spliceosomal P complex|NTC associated proteins

Basic information

Region (hg38): 16:2752626-2772538

Links

ENSG00000167978 ∙ NCBI:23524 ∙ OMIM:606032 ∙ HGNC:16639 ∙ Uniprot:Q9UQ35 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, autosomal dominant 72 (Strong), mode of inheritance: AD
• intellectual developmental disorder, autosomal dominant 72 (Definitive), mode of inheritance: AD
• intellectual developmental disorder, autosomal dominant 72 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 72	AD	General	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	Craniofacial; Neurologic	35567594; 37212523; 37272925

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SRRM2 gene.

• Inborn_genetic_diseases (674 variants)
• not_provided (244 variants)
• not_specified (33 variants)
• Intellectual_developmental_disorder,_autosomal_dominant_72 (33 variants)
• Neurodevelopmental_disorder (23 variants)
• SRRM2-related_disorder (23 variants)
• Status_epilepticus (1 variants)
• SRRM2-related_Neurodevelopmental_disorder (1 variants)
• Seizure (1 variants)
• Complex_febrile_seizure (1 variants)
• Neurodevelopmental_abnormality (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SRRM2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016333.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				41	7	48
missense	1	1	712	131	11	856
nonsense	15	8	2			25
start loss						0
frameshift	21	9	4			34
splice donor/acceptor (+/-2bp)	1		1			2
Total	38	18	719	172	18

Highest pathogenic variant AF is 0.00000657272

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SRRM2	protein_coding	protein_coding	ENST00000301740	14	20210

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.49e-13	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-6.28	2410	1.68e+3	1.43	0.000120	17102
Missense in Polyphen		276	238.17	1.1588		2512
Synonymous	-13.2	1030	615	1.67	0.0000360	6516
Loss of Function	9.16	7	111	0.0628	0.00000949	1060

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000424	0.000297
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000109	0.000105
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in pre-mRNA splicing. May function at or prior to the first catalytic step of splicing at the catalytic center of the spliceosome. May do so by stabilizing the catalytic center or the position of the RNA substrate (By similarity). Binds to RNA. {ECO:0000250, ECO:0000269|PubMed:10668804}.
• Pathway: Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.235

Intolerance Scores

• loftool: 0.174
• rvis_EVS: -4.51
• rvis_percentile_EVS: 0.08

Haploinsufficiency Scores

• pHI: 0.101
• ghis: 0.562

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.699

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Srrm2

Gene ontology

• Biological process: mRNA splicing, via spliceosome
• Cellular component: nucleus;nucleoplasm;Cajal body;nuclear speck;U2-type catalytic step 2 spliceosome;catalytic step 2 spliceosome
• Molecular function: RNA binding;protein N-terminus binding;C2H2 zinc finger domain binding