SYCE2

Chr 19

synaptonemal complex central element protein 2

Also known as: CESC1

NCBI Gene: 256126 ENSG00000161860 UniProt: Q6PIF2 OMIM: 611487

The encoded protein is a major component of the synaptonemal complex that forms between homologous chromosomes during meiosis and associates with SYCP1 and SYCE1 to facilitate chromosome synapsis. Mutations cause autosomal recessive male infertility due to nonobstructive azoospermia, with affected males showing meiotic arrest and impaired spermatogenesis. This gene has moderate constraint against loss-of-function variants (LOEUF 0.63), consistent with its essential role in male fertility.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is part of the synaptonemal complex formed between homologous chromosomes during meiotic prophase. The encoded protein associates with SYCP1 and SYCE1 and is found only where chromosome cores are synapsed. [provided by RefSeq, Dec 2012]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.63

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.63LOEUF

pLI 0.281

Z-score 2.45

OE 0.24 (0.11–0.63)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.93Z-score

OE missense 0.76 (0.64–0.91)

92 obs / 120.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.11–0.63)

0≤0.351.4

Missense OE?0.76 (0.64–0.91)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 3 / 12.3Missense obs/exp: 92 / 120.9Syn Z: 1.13

Background carrier burden — how many people carry a rare variant somewhere in SYCE2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 260

232 rare PASS variants

Rare truncating (LoF)

1 in 8,800

16 rare PASS variants

Rare synonymous (reference)

1 in 380

98 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SYCE2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 510	1 in 10,000
South Asian	~43k	1 in 120	≈ 1 in 43,000
Remaining (unassigned)	~30k	1 in 180	none seen
European (Finnish)	~27k	1 in 480	1 in 5,300
Admixed American	~22k	1 in 180	≈ 1 in 7,300
African / African American	~21k	1 in 240	≈ 1 in 4,400
East Asian	~20k	1 in 160	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 2,600	none seen
Middle Eastern	~2,884	1 in 350	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 6 coding exons well covered in gnomAD exomes and genomes.? see exons ↓