SYCP2

protein-coding

synaptonemal complex protein 2

Gene summary

The synaptonemal complex is a proteinaceous structure that links homologous chromosomes during the prophase of meiosis. The protein encoded by this gene is a major component of the synaptonemal complex and may bind DNA at scaffold attachment regions. The encoded protein requires synaptonemal complex protein 3, but not 1, for inclusion in the synaptonemal complex. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014258.4

Inheritance

ClinVar variants

P:6U:188B:30

Top phenotype

Spermatogenic failure 1

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr20:59,863,564-59,933,655

External References & Databases

Ensembl (ENSG00000196074)

Transcript & Mutation Effects

hg38 • Region Span ~70.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0009776

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Spermatogenic failure 1AD

Manifestation: Endocrine; Genitourinary

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: 31866047

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SYCP2 variants in ClinVar

9 Conditions Cataloged

not specifiedTotal: 188

not providedTotal: 19

Oligosynaptic infertilityTotal: 6

Non-obstructive azoospermiaTotal: 3

SYCP2-related disorderTotal: 3

CryptozoospermiaTotal: 2

Prostate cancerTotal: 1

Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014258.4. 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				9 clinvar	3 clinvar	12
missense			178 clinvar	12 clinvar	6 clinvar	196
nonsense			3 clinvar			3
start loss						0
frameshift		4 clinvar				4
splice donor/acceptor (+/-2bp)		2 clinvar	7 clinvar			9
Total	0	6	188	21	9	224

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014258.4	RefSeq	NP_055073.2	43	MANE Select
ENST00000357552.8	Ensembl	ENSP00000350162.2	43	MANE Select
ENST00000371001.6	Ensembl	ENSP00000360040.2	43	Standard
ENST00000371001.7	Ensembl	ENSP00000360040.2	43	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Reproduction
Meiotic synapsis
Meiosis
Cell Cycle

Biological Process

synaptonemal complex assembly
male meiotic nuclear division
female meiotic nuclear division
fertilization
negative regulation of apoptotic process

Molecular Function

DNA binding
protein heterodimerization activity

Cellular Component

synaptonemal complex
lateral element
nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000357552
Coding exons: 43
Length: 70093
Individuals with no LoFs: 125675
Homozygous LoFs: 0
Heterozygous LoFs: 34
Defined: 125709
p: 0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.258	691	710	0.973	0.0000340	10180
Missense (PolyPhen)		144	188.15	0.76535		2942
Synonymous	-0.507	246	236	1.04	0.0000118	2576
Loss of Function	7.69	9	86.0	0.105	0.00000411	1226

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00025	0.00024	rare
South Asian	0.000068	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Major component of the axial/lateral elements of synaptonemal complexes (SCS) during meiotic prophase. Plays a role in the assembly of synaptonemal complexes. Required for normal meiotic chromosome synapsis during oocyte and spermatocyte development and for normal male and female fertility. Required for insertion of SYCP3 into synaptonemal complexes. May be involved in the organization of chromatin by temporarily binding to DNA scaffold attachment regions. Requires SYCP3, but not SYCP1, in order to be incorporated into the axial/lateral elements. {ECO:0000250|UniProtKB:Q9CUU3}.;

Recessive Scores

pRec: 0.401

Intolerance Scores

LoFtool: 0.557
RVIS EVS: 0.92
RVIS percentile EVS: 89.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Indispensability pred.: N
Indispensability score: 0.163

Gene Damage Prediction

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