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

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.

• Neurodevelopmental disorder (19 variants)
• Intellectual developmental disorder, autosomal dominant 72 (8 variants)
• not provided (2 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.

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				24	11	35
missense			346	34	11	391
nonsense	9	2	3			14
start loss						0
frameshift	13	5	5			23
inframe indel			7	2	1	10
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	22	7	361	61	23

Variants in SRRM2

This is a list of pathogenic ClinVar variants found in the SRRM2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-2756378-T-C			Uncertain significance (Jul 22, 2024)
16-2756387-C-T		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
16-2756422-C-T		Neurodevelopmental disorder	Pathogenic (Jan 11, 2022)
16-2756440-G-C		Inborn genetic diseases	Uncertain significance (Jul 14, 2023)
16-2756443-C-G		Inborn genetic diseases	Uncertain significance (Oct 06, 2022)
16-2756443-C-T		Inborn genetic diseases	Uncertain significance (Apr 25, 2022)
16-2756444-G-C			Uncertain significance (Nov 11, 2023)
16-2756447-GC-G			Uncertain significance (May 01, 2024)
16-2756450-G-T		Inborn genetic diseases	Uncertain significance (Jan 03, 2022)
16-2756461-C-T		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)
16-2756464-C-T		Inborn genetic diseases	Uncertain significance (Oct 21, 2024)
16-2756473-A-G		Neurodevelopmental disorder	Uncertain significance (Jul 16, 2023)
16-2756500-G-T			Pathogenic (Mar 22, 2023)
16-2756524-A-T			Uncertain significance (Feb 17, 2023)
16-2756527-C-G		Inborn genetic diseases	Uncertain significance (Jun 29, 2023)
16-2756560-G-A		Inborn genetic diseases	Uncertain significance (Aug 08, 2023)
16-2756591-T-C			Uncertain significance (Apr 15, 2024)
16-2757512-C-G			Uncertain significance (Feb 13, 2024)
16-2757513-G-A			Uncertain significance (Mar 20, 2023)
16-2757546-G-A		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
16-2757548-G-GGCAAGGA			Pathogenic (Sep 01, 2024)
16-2757556-G-A			Likely benign (Jun 08, 2017)
16-2757567-G-GGC		SRRM2-related disorder	Likely pathogenic (Jul 14, 2023)
16-2757792-C-G		Inborn genetic diseases	Uncertain significance (Sep 30, 2024)
16-2757834-T-C		Inborn genetic diseases	Uncertain significance (Aug 05, 2024)

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